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OBM Neurobiology

(ISSN 2573-4407)

OBM Neurobiology is an international peer-reviewed Open Access journal published quarterly online by LIDSEN Publishing Inc. By design, the scope of OBM Neurobiology is broad, so as to reflect the multidisciplinary nature of the field of Neurobiology that interfaces biology with the fundamental and clinical neurosciences. As such, OBM Neurobiology embraces rigorous multidisciplinary investigations into the form and function of neurons and glia that make up the nervous system, either individually or in ensemble, in health or disease. OBM Neurobiology welcomes original contributions that employ a combination of molecular, cellular, systems and behavioral approaches to report novel neuroanatomical, neuropharmacological, neurophysiological and neurobehavioral findings related to the following aspects of the nervous system: Signal Transduction and Neurotransmission; Neural Circuits and Systems Neurobiology; Nervous System Development and Aging; Neurobiology of Nervous System Diseases (e.g., Developmental Brain Disorders; Neurodegenerative Disorders).

OBM Neurobiology publishes a variety of article types (Original Research, Review, Communication, Opinion, Comment, Conference Report, Technical Note, Book Review, etc.). Although the OBM Neurobiology Editorial Board encourages authors to be succinct, there is no restriction on the length of the papers. Authors should present their results in as much detail as possible, as reviewers are encouraged to emphasize scientific rigor and reproducibility.

Publication Speed (median values for papers published in 2024): Submission to First Decision: 7.6 weeks; Submission to Acceptance: 13.6 weeks; Acceptance to Publication: 6 days (1-2 days of FREE language polishing included)

Current Issue: 2025  Archive: 2024 2023 2022 2021 2020 2019 2018 2017
Open Access Review

Neurotoxicity Following Exposure to Micro and Nanoplastics

Mojtaba Ehsanifar 1,*, Zeinab Yavari 2

  1. Department of Environmental Health, Torbat Jam Faculty of Medical Sciences, Torbat Jam, Iran

  2. Department of Civil and Architectural Engineering, College of Engineering, Sultan Qaboos University, Muscat, Oman

* Correspondence: Mojtaba Ehsanifar

Academic Editor: Lynne Ann Barker

Collection: New Developments in Brain Injury

Received: December 13, 2024 | Accepted: March 04, 2025 | Published: March 16, 2025

OBM Neurobiology 2025, Volume 9, Issue 1, doi:10.21926/obm.neurobiol.2501277

Recommended citation: Ehsanifar M, Yavari Z. Neurotoxicity Following Exposure to Micro and Nanoplastics. OBM Neurobiology 2025; 9(1): 277; doi:10.21926/obm.neurobiol.2501277.

© 2025 by the authors. This is an open access article distributed under the conditions of the Creative Commons by Attribution License, which permits unrestricted use, distribution, and reproduction in any medium or format, provided the original work is correctly cited.

Abstract

The pervasive presence and enduring existence of micro and nanoplastics in the environment render their exposure to humans and aquatic creatures unavoidable. Research indicates these tiny plastic particles can be taken in by aquatic beings and mammals. Once within the body, micro and nanoplastics have the capability to infiltrate the brain, although the level of penetration and the subsequent neurotoxic effects are not fully explored. Previous studies indicate that metal (oxide) nanoparticles can enter the brain and induce neurotoxic effects. Given the chemical resemblances between plastic particles and inert metal (oxide) nanoparticles, this review aims to summarize existing studies on the neurotoxic implications of nanoplastics across various species and in vitro settings. The current evidence, although incomplete, suggests that exposure to nanoplastics may lead to oxidative stress, potentially causing cell damage and raising the risk of developing neurological disorders. Moreover, such exposure could inhibit acetylcholinesterase activity and alter neurotransmitter levels, potentially contributing to observed behavioral changes. There is a notable lack of systematic comparison regarding the neurotoxic effects stemming from different particle types, shapes, and sizes at various concentrations and durations of exposure. Understanding these aspects is essential for further evaluating the neurotoxic danger and risk associated with nanoplastics.

Graphical abstract

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Keywords

Neurotoxicity; microplastic; nanoplastic; oxidative stress; nanoparticles

1. Introduction

Plastics are crucial in producing various products, including packaging materials, pharmaceuticals, cosmetics, textiles, masks, and surgical instruments [1,2,3]. Their widespread application can be attributed to their adaptability, strength, water resistance, cost-effectiveness, and ease of production with minimal energy use [1,2]. These attributes make plastics an excellent choice for fabricating medical devices such as syringes, IV bags, medical packaging, artificial joints, and prosthetics, as well as food storage solutions and other plastic goods [4]. Despite these benefits, plastics face criticism due to environmental and health concerns stemming from their long-lasting nature, widespread presence, and potential to contaminate food and water sources for animals [1,4]. Plastics gained traction alongside the Industrial Revolution, expanding significantly as a consumer product since the 1930s and 1940s. Between 1975 and 2012, global plastic resin production jumped by 620%, reaching 288 million tons [5]. Consequently, plastic waste surged from 275 million tons in 2010 to 335 million tons by 2017 [5,6], posing a grave threat to human health due to its largely unsustainable usage patterns [4]. In the U.S., the recycling rate for plastics is merely 8.8% [7]. Plastics' slow decomposition remains problematic, as single-use plastics like LDPE bags may take up to 250 years to break down in landfills or natural environments [8]. By 2025, it is expected that 192 countries' coasts within 50 km will accumulate around 250 million tons of poorly managed marine plastic waste [5]. Over time, these enduring plastics fragment into microplastics and nanoplastics—tiny particles with variable chemical structures formed through degradation processes [9,10,11]. Microplastics and nanoplastics, present everywhere, from the atmosphere to aquatic systems, pose threats due to their minute size and diverse shapes, including fibers, foams, beads, and fragments [12]. Interestingly, spherical microplastics may cause fewer gut health issues than irregular ones [13]. Although there is debate over the size categories of plastic debris, classifications typically include macroplastics (2.5-100 cm), mesoplastics (0.1-2.5 cm), microplastics (1000 μm–1 µm), and nanoplastics (<1 µm) [14,15,16], with some sources defining micro- and nanoplastics as slightly different ranges “small microplastics” (1 µm to <100 µm), “sub-micron plastics” (100 nm - <1 µm), “nanoplastics” (1 nm to <100 nm) [17,18], or 100 nm–1 nm [19,20]. However, there is a significant gap in understanding regarding the dimensions, architecture, and cost of micro- and nanoplastics. The toxicological impacts of micro- and nanoplastics on human organs, their cellular absorption pathways, and the underlying molecular mechanisms remain underexplored due to the scant and often inconsistent scientific literature. This study aims to provide an overview of the potential entry of microplastics and nanoplastics into the body and then into the brain and to link exposure and the physicochemical properties of the particles with neurological diseases. In addition, it also provides insights into the mechanisms of the effects of microplastics and nanoplastics on the diseases above.

2. Methodology

A systematic search was conducted across multiple databases, including PubMed, Scopus, and Web of Science, using keywords such as combinations such as Neurotox AND Nanoplastic, Neurotox AND Microplastic, and Neurotox AND plastic particles, neuroinflammation, and oxidative stress markers. The review includes studies published between 2015 and 2024, ensuring that the most current findings are represented. The inclusion criteria were focused on peer-reviewed articles that involved both animal and human models and specifically examined micro and nanoplastics’s effects on oxidative stress and neuroinflammation. Studies unrelated to micro and nanoplastics, those involving other pollutants classes, or those lacking molecular insights were excluded. The selected studies were synthesized to assess consistent findings on micro and nanoplastics’s ability to induce oxidative stress, including the production of reactive oxygen species (ROS) and lipid peroxidation, as well as its endocrine-disrupting effects on the hypothalamic-pituitary-adrenal (HPA) axis, thyroid function, and other hormonal pathways. Special attention was given to studies addressing micro and nanoplastics’s persistence in the environment and their potential for cumulative toxicity through prolonged exposure.

3. Comparison with Prior Studies

While micro and nanoplastics’s toxicological effects have been well documented, previous reviews have not thoroughly addressed micro and nanoplastics’s interaction with other environmental contaminants or its long-term impact at sub-lethal doses. This review fills these gaps by focusing on micro and nanoplastics’s dual role in oxidative stress and endocrine disruption. It also provides a more detailed exploration of micro and nanoplastics’s molecular mechanisms, which have mainly been underexplored in earlier work. The integration of recent findings on micro and nanoplastics’s environmental persistence and the risks of chronic exposure further distinguishes this review from past analyses, offering a more comprehensive understanding of micro and nanoplastics toxicity.

4. Ways to Microplastics and Nanoplastics Exposure

Recently, the frequent use of plastic has been pinpointed as a substantial contributor to micro and nanoplastics pollution, capturing the focus of environmentalists and medical scholars [21]. This pollution is a pressing global issue due to its threat across ecosystems. It includes humans, who face exposure through food, drinking water, inhaled air, and skin contact via cosmetic and pharmaceutical products [22]. Research indicates that micro- and nanoplastics are harmful in environmental and laboratory contexts, impacting experimental animal models, cellular assays, and various aquatic and land animal species [23,24,25]. Humans face exposure to these micro- and nanoplastics predominantly through consuming marine animals and other food commodities contaminated with these particles, including everyday consumer products like toothpaste, beer, honey, salt, and sugar [26,27]. In addition to food sources, humans ingest these plastics through water consumption, mainly mineral and drinking water stored in plastic bottles and cartons [26,27]. Beyond ingestion, inhalation poses another exposure route, as micro- and nanoplastics can be released from textiles, synthetic rubber tires, and plastic coatings [26,27,28]. Rodent studies over the years have documented the presence of these minuscule particles, particularly those 0.3 μm or smaller, which have been shown to transit to vital organs like the liver and spleen, and systems like the lymphatic system, though at minimal levels [29,30,31]. There is compelling evidence indicating that micro-scale plastic fibers have made their way into human lung tissues, implying the possibility of these micro- and nanoplastic particles entering the body through inhalation processes [32,33]. This concern extends further, as certain studies have documented the slight absorption of biodegradable polymeric microparticles when ingested via the gastrointestinal tract [34]. While these investigative efforts collectively underscore the potential for micro- and nanoplastic entry into the human body through both inhalation and ingestion [35], there remains a significant shortfall in research that meticulously examines how these particles are dispersed throughout the body, specifically across various organs, based on differences in particle dose and size. Moreover, the health implications associated with exposure to, absorption of, and the transport mechanisms of micro- and nanoplastics within the human body have not been thoroughly explored, making this a central issue in current scientific discussions and debate [24,26,36].

5. Microplastics and Nanoplastics Effects on the Nervous System

Due to the constraints in obtaining human tissue samples, the repercussions of microplastics and nanoplastics on human health remain inadequately comprehended [37]. The human nervous system, a sophisticated network with numerous neurons, oversees various physiological functions [38]. Despite the limited research on how microplastics and nanoplastics impact the nervous system, there is potential for nanoplastics to breach physiological barriers like the BBB [39]. The transport and build-up of these particles in the brain can result in different types of damage, heightening the brain's susceptibility to neurological disorders by causing oxidative stress [40]. Research indicates that microplastics and nanoplastics have detrimental effects on the nervous system, potentially leading to neurodegeneration. Studies have observed that nanoplastics contribute to neurotoxicity by disrupting typical neuron arrangements and characteristics in the cerebral cortex, signified by nuclear pyknosis. In particular, mouse brain tissues exposed to PS-NH2 showed increased caspase-3 signals, a marker for neuron cell apoptosis. Additionally, cytokines like TNF-α and IL-6 were upregulated in these tissues, hinting at inflammation caused by cytokine presence [41]. In the case of European seabass, exposure to microplastics reduced the release of the enzyme acetylcholinesterase (AChE), triggered oxidative stress and lipid peroxidation, and forced a shift towards anaerobic energy pathways, which subsequently led to irregular swimming behavior [42]. When neural cells were subjected to these particles, toxicity was induced and the metabolic rate decreased. These adverse effects of microplastics and nanoplastics appear to stem from the build-up of immune cells activated within the brain, oxidative stress, and heightened levels of inflammatory cytokines in circulation, particularly TNF-α and IL-6 [41,43]. Other research supports the neurotoxic impact of these particles [44,45], such as findings by O'Donovan et al., [46] which demonstrated that LDPE microplastic particles in clams could lead to neurotoxicity by altering acetylcholinesterase activity or by infiltrating the brain and causing oxidative stress, culminating in cellular damage that can cause neurodegenerative and neurodevelopmental issues [47].

6. Neurotoxicity of Nanoparticles

Metal (oxide) nanoparticles are prevalent in various fields, including food production, personal care products, cosmetics, and biomedical therapy, where they're utilized for drug delivery and gene therapy [48,49,50,51]. The impact of these nanoparticles has been extensively studied, with the central nervous system identified as a crucial target for their toxic effects [52,53,54]. These nanoparticles can infiltrate the brain, primarily by traversing the blood-brain barrier (BBB) or through retrograde transport via the olfactory nerve endings [47,55,56,57]. The properties of different metal and metal oxide nanoparticles vary widely; intriguingly, some of their physicochemical properties are akin to those observed in plastic particles. Notably, specific metal nanoparticles exhibit high reactivity, capable of inciting oxidative stress and subsequent damage. Notable examples include iron oxide [58,59], silver [60,61], and copper oxide [62,63]. Gold (Au) and titanium dioxide (TiO2) nanoparticles closely align with the criteria for hemistry. This is a critical trait when evaluating metal (oxide) nanoparticles alongside plastic micro- and nanoparticles [28,64,65]. Studies have demonstrated that gold nanoparticles can penetrate brain tissues in adult zebrafish and rats. Within these tissues, they are capable of causing oxidative stress, altering energy and mitochondrial metabolism, affecting acetylcholinesterase (AChE) activity, and influencing neurobehavioral functions [66,67,68].

Similarly, among the various types of TiO2 nanoparticles, the most extensively researched are those that enter the brains of aquatic creatures like fish. Here, they can trigger oxidative damage, increase cell mortality, impact neurotransmitter levels, affect motor activity, and alter spatial recognition abilities [69,70,71,72]. In rodent models, exposure through the oral, intranasal, or intratracheal routes to TiO2 nanoparticles (sizing between 5 to 100 nm) has been linked to oxidative stress and neuroinflammation [73,74]. Such exposure disrupts glutamatergic pathways, modifies neurotransmitter levels [73,75,76], changes AChE activity [74,75], hinders motor skills [77], reduces long-term potentiation, and hampers learning and memory recall [75,78]. Further in vitro experiments have reinforced the capability of TiO2 nanoparticles to incite oxidative stress and neuroinflammation [79,80,81,82]. Despite specific effects of gold and TiO2 nanoparticles being observed only after substantial doses or non-natural administration methods (like injections), these nanoparticles can nonetheless reach the brain and impose an array of neuroprotective impacts. The degree to which these findings are relevant to micro- and nanoplastics remains largely unexplored. Given the prevalent nature of micro- and nanoplastics and considering the evident neurotoxic effects tied to gold and TiO2 nanoparticles of comparable size and chemical neutrality, this review delves into the potential of these plastics to offer neuroprotection.

7. Microplastics and Nanoplastics Neurotoxic Effects on Marine Invertebrates

Caenorhabditis elegans were subjected to five different spherical polystyrene microplastic sizes (0.1–5 μm) in a culture medium at 1 mg/L concentration. This led to excitotoxicity affecting their movement, lowered survival rates, and decreased average lifespan, with the most pronounced effects observed with exposure to 1.0 μm size particles. Additionally, the expression of several neuronal genes declined, which was linked to disruptions in cholinergic and GABA neurons and increased oxidative stress. However, there is no direct proof of the ingestion of these microplastics by C. elegans [83,84]. Earthworms (Eisenia fetida) exposed to low-density polyethylene particles ranging from 100–200 μm (0.1–1.5 g/kg soil) for a period of up to 28 days within artificial soil, exhibited skin damage, particularly at 1.5 g/kg soil exposure level. Upon analyzing and quantifying polyethylene particles, their uptake (after 14–28 days at 1.5 g/kg soil) was confirmed, yet the detailed distribution of the particles inside the earthworms remains unclear. When exposed to polyethylene particles at a level of 1.0 g/kg soil for 28 days, an increase in catalase activity and malondialdehyde levels was noted, suggesting oxidative stress in these organisms. Notably, exposure levels of 1.0 and 1.5 g/kg soil for 21 and 28 days, respectively, also led to higher AChE activity [85]. Freshwater zebra mussels, known as Dreissena polymorpha, were exposed to pristine polystyrene microbeads of two sizes (1 μm and 10 μm) at concentrations of 1 and 4 × 106 MPs/L for six days. This led to the accumulation of particles within the gut lumen and further movement to tissues and hemolymph, as observed with confocal microscopy. Importantly, these polystyrene microbeads did not cause genotoxic effects. While both bead sizes boosted dopamine levels, other parameters such as serotonin, glutamate levels, and activities of monoamine oxidase and AChE remained unchanged. Interestingly, the lower-dose mix enhanced catalase activity, lowering glutathione peroxidase and pointing towards moderate cellular stress [86]. In a different study involving the bivalve Scrobicularia plana, exposure to 20 μm polystyrene microplastics at a concentration of 1 mg/L resulted in particles being detected in the hemolymph, digestive gland, and gills using light microscopy and infrared spectroscopy. A 7-day exposure to these microplastics in the gills led to sustained increases in superoxide dismutase (SOD) activity and a rise in Glutathione-S-transferase (GST) activity by the end of the exposure, suggesting oxidative stress. During the exposure period of 3 to 14 days, along with post-excretion, a decrease in AChE and lipid peroxidation (LPO) activities was noted in the gills. In the digestive gland, from day 14, SOD activity was elevated, whereas catalase activity was reduced [87]. Myetilus gallopro-vincialis (Mediterranean Mussels) were subjected to polystyrene microplastics (0.11 μm, 0.005–50 mg/L) for 96 hours, resulting in notable deviations in the genes' expression linked to biotransformation, cellular stress response, and innate immunity. Distinct responses were observed in the gills (hsp70 at 50 mg/L) and digestive glands (cyp11 at 0.5 mg/L, cyp32 at 5 mg/L, cat at 0.05 and 0.5 mg/L, lys at 5 mg/L). While there wasn't an evident pattern of dose dependence, the mean DNA damage increased with exposure concentrations ranging from 0.05–50 mg/L. There was a reduced cholinesterase activity in the hemolymph at concentrations between 0.05–0.5 mg/L, though no further signs of neurotoxicity were noted. However, there’s a lack of evidence concerning the actual uptake of polystyrene microplastics [88]. Exposure of the same species to both unpolluted and pyrene-contaminated polyethylene and polystyrene microplastics (100 μm, 1.5 g/L) over seven days led to the introduction of plastic particles within the hemolymph, gills, and intestines, identified through polarized light microscopy. This exposure decreased AChE activity in the gills but not in the hemolymph, also inducing nuclear alterations and DNA damage. Pyrene did not amplify the AChE activity inhibition [89]. Corbicula flumina (Asian Freshwater Mussels), when exposed to red fluorescent polymeric microspheres (composition unspecified; 1–5 μm, 0.2 or 0.7 mg/L) for 96 hours, showed plastic particles inside the digestive tract, gland’s lumen, connective tissue, hemolymphatic sinuses, and the surface of the gills using light and fluorescent microscopy. Exposure at 0.2 mg/L significantly reduced cholinesterase activity, heightened with florfenicol exposure [90]. In another study, these mussels exposed to red fluorescent polymeric microspheres (1–5 μm, 0.13 mg/L) for eight days had increased presence of particles in their digestive tract and gills. The exposure diminished cholinesterase activity and elevated LPO levels, signifying oxidative damage. The effects were reversible after six days of recovery and, surprisingly, were mitigated by simultaneous mercury exposure [91]. The exposure of both striped shrimp (Amphibia lanu amphitrite) and brine shrimp (Artemia Franciscan) larvae to 0.1 μm fluorescent polystyrene microparticles, at concentrations ranging from 0.001 to 10 mg/L, over periods of 24 to 48 hours led to plastic particles being detectable within them through fluorescence microscopy. Yet, it remains uncertain whether these particles can penetrate further into surrounding tissues. When exposed to microplastics at concentrations of 1 mg/L or higher for 48 hours, noticeable alterations in the larvae's swimming speeds were observed. Furthermore, the microplastic exposure resulted in various influences on enzyme activities. Notably, there was a significant increase in catalase activity, more evident at a higher concentration of 1 mg/L. In contrast, the influence on cholinesterases, such as acetylcholinesterase and propionylcholinesterase, showed no clear pattern of dose dependency [92].

Exposure of brine shrimp larvae (Artemia Francesca) to amino-modified polystyrene nanoparticles, with a size of 50 nm, at concentrations of 0.1 to 10 μg/mL over either 48 hours or 14 days caused a decrease in GST and catalase activity. This reduction suggests oxidative stress, along with inhibition of carboxylation and ChE carboxylation processes, particularly at a 1 μg/mL concentration. Unfortunately, despite these effects, there was no substantial evidence to confirm the actual uptake of these polystyrene nanoparticles by the larvae [93].

8. Microplastics and Nanoplastics Neurotoxic Effects in Rodents

In contrast to the extensive rodent in vivo research available for metal(oxide) nanoparticles, studies delving into the micro- and nanoplastics neurotoxicity in rodents are notably scarce, with only two such investigations. This scarcity is particularly surprising when considering the documented neurotoxic consequences of micro- and nanoplastics exposure in marine and fish invertebrates. In the solely published mice in vivo study, adult mice were subject to chronic exposure over 30 days to polystyrene microplastics, with sizes of 5 and 20 μm and doses ranging from 0.01 to 0.5 mg per day (approximately 0.5 to 25 mg/kg body weight daily), administered through oral gavage. The exposure to polystyrene microplastics led to the absorption and presence of particles in the mice's gut, liver, and kidneys, confirmed via fluorescence spectrometer analysis of freeze-dried tissues. During the initial week of exposure, particle concentrations in the tissues rose swiftly and stabilized at approximately 0.2, 1.0, and 1.4 mg/g for 5 μm particles in the liver, kidney, and gut, respectively. For 20 μm particles, the concentration was more consistent across the organs, reaching a plateau at about 0.8. Examination of the liver revealed dose-dependent alterations in energy metabolism, including reduced ATP levels and elevated LDH activity, alongside oxidative stress markers such as increased GSH-Px and SOD and decreased CAT. Curiously, liver AChE activity rose, and metabolomic shifts implied possible neurotransmitter level changes. Notably, the difference in effect size between 5 μm and 20 μm particles was minimal when considered on a mass basis. Regrettably, the study did not explore brain tissue [42]. Another in vivo study involved chronic exposure, over five weeks, of male rats to significant doses of polystyrene nanoplastics measuring 40 nm, with dosages between 1 and 10 mg/kg body weight per day. However, this exposure did not impact behavior or weight gain, and no evidence was provided of actual polystyrene nanoplastic uptake [94].

9. Factors Affecting the Microplastics and Nanoplastics Neurotoxic Potential

Several factors can affect the neurotoxic potential of micro- and nanoplastics. One major factor is the extent of exposure organisms have to these particles, significantly impacting the potential neurotoxic effects [95]. In real-life scenarios, the levels of exposure are notably lower than those typically used in laboratory experiments. Conversely, the length of exposure in experimental situations is usually far less than what would be encountered in human exposures. Some research indicates that the neurotoxic impacts of micro- and nanoplastics are dependent on how long one is exposed [93,96,97]. Besides concentration and exposure time, the temperature at which exposure occurs may also play a role in neurotoxicity, especially in fish, with toxicity levels rising as temperatures increase [98,99]. Apart from these locational factors, the intrinsic properties of the particles themselves may heavily influence their neurotoxic potential. Particle size is considered one of the key characteristics influencing toxicity, with nanoparticles generally being absorbed more readily and have more significant toxicity than microparticles [95,100]. However, for plastic particles specifically, there is only limited data supporting the idea that smaller particles exhibit higher toxicity [42,83,101]. The hydrodynamic diameter of particles, reflecting the size of secondary particles, could play a significant role in their neurotoxic effects. Though smaller particles tend to exhibit more significant neurotoxicity, they are also prone to aggregation, forming larger clusters. While this aggregation theoretically mitigates neurotoxic potential by increasing the particle size, there is limited research on this phenomenon. Notably, a study discovered that nanoplastics aged for six months expanded from 65 nm to over 1300 nm, amplifying toxicity in comparison to the initial particles, implying that larger aggregated particles might exhibit increased neurotoxicity [102]. The extent of particle aggregation is influenced by surface charge and the suspension medium [71,79,80,92,93]. Moreover, a particle's surface charge is directly implicated in its neurotoxic potential and biological activity, whether micro- or nanoplastics [28,65]. Specifically, nanoparticles with a negative surface charge tend to undergo greater cellular uptake [103], whereas a positive charge leads to increased disruption of the plasma membrane and more significant mitochondrial harm [104]. Unfortunately, scant research analyzing the micro- and nanoplastics surface charge investigations into this aspect remains nascent. The particles' zeta potentials span from +40 mV to -50 mV, yet their neurotoxic implications are beginning to be examined. For metal (oxide) particles, the elemental composition has a bearing on toxicity. Likewise, the specific chemical makeup of micro- and nanoplastics is anticipated to influence their neurotoxic potential. The shape of plastic particles, though not exhaustively compared, could substantially impact neurotoxic potential. Variations in shape—such as spheres, fibers, and rods—lead to differences in surface area and potential internalization [65]. Therefore, comprehensive research is necessary for comparing neurotoxic effects across various particle types, shapes, and sizes, considering aggregation impacts, through both in vitro and in vivo model systems. Another complexity is the potential for microplastics and nanoplastics to act as carriers for pathogens and chemicals. Although not fully understood, these particles may adsorb different environmental substances [105] and potentially even pathogens [106]. These adsorption capabilities might inadvertently enhance exposure to these harmful agents, aggravating their neurotoxic impact. Therefore, further investigation is essential to elucidate the detailed role of these factors in particle-induced neurotoxicity.

10. Mechanisms of Microplastics and Nanoplastics Entry into the Brain

Micro- and nanoplastics predominantly infiltrate the brain by traversing the BBB through a permeation process [107]. Generally, micro- and nanoplastic internalization involves two primary mechanisms: passive permeation and active endocytosis, which include pinocytosis and phagocytosis [108]. Endocytosis can proceed through kaolin-mediated pathways (typically for larger particles) and clathrin-mediated pathways (typically for small nanoplastics) [109]. The permeation processes of micro- and nanoplastics are affected by their physicochemical characteristics, such as the shape and size of the particles, their chemical makeup, and their surface charge [110,111]. There's minimal research regarding how nanoplastic size affects their penetration through the BBB. This is primarily because conducting such experiments is complex, requiring labeled nanoplastics of varying sizes to be detectable within the intricate environments of biological systems [112]. Research has demonstrated that smaller, fluorescently labeled polystyrene particles (100 nm) can more effectively penetrate the brain of zebrafish embryos compared to larger particles (500 and 1000 nm), leading to increased entry and neurotoxicity of the smaller particles [113]. In the domains of medical and environmental research, numerous studies have utilized various metal nanomaterials to demonstrate the crucial role that particle size plays in the capacity of these nanomaterials to traverse the BBB [111]. For example, one investigation established that smaller-sized nanoplastics more readily infiltrate the brain, posing greater toxicity than larger microplastics [114]. Another study assessed different sizes of silica nanomaterials regarding their ability to pass through brain endothelial cells in mice [115]. The findings indicated that smaller particles, specifically those measuring 25 nm, were absorbed by the brain more effectively than those measuring 50 nm and 100 nm [109,116]. It has been posited that larger nanomaterials mainly penetrate using active mechanisms such as pinocytosis and phagocytosis. While applying this knowledge directly to nanoplastics is debatable because of variations in particle chemistry and density—factors that greatly influence cellular penetration—these investigations provide a foundational comprehension and form a basis for conducting comparable experiments with nanoplastics [117]. The configuration of nanoplastics also has potential ramifications on their penetration through the BBB into the brain, as it can influence their interaction with cellular structures. Research has examined the toxic effects of both spherical and rod-shaped polystyrene nanoplastics in mice. Findings demonstrate that rod-shaped nanoplastics may exhibit a more robust binding ability than their spherical counterparts [118]. Further evidence regarding the influence of particle shape on BBB penetration exists for other nanoparticles. For instance, a study highlighted that gold rod-shaped nanomaterials possess a heightened affinity and efficiency for endothelial cells, leading to increased uptake [119]. An essential factor affecting the ability of nanoplastics to bypass the BBB is their chemical structure. This aspect also helps distinguish between various types of nanoparticles. Recent investigations indicate that nanoplastics made from polystyrene and polyvinyl chloride (PVC) can move across the BBB, albeit at minimal concentrations. The research further highlights that a biological corona, comprised of proteins and metabolites, significantly alters the permeability efficiency of these nanomaterials through the BBB. The corona’s development is directly influenced by the particle's chemical attributes [39]. Studies have also demonstrated that polypropylene, polyethylene, polystyrene, and PVC can access the central nervous system (CNS), with polypropylene and polyethylene possibly inducing greater inflammation [120]. Chemical composition, even with identical particle sizing, can differentially impact the behavior of zebrafish embryos [121]. This recognition complicates efforts to comprehend how the composition may affect the biological outcomes and toxicity of nanoparticles [122]. The particles' surface charge is crucial in defining their capacity to penetrate the BBB. Nanoplastics with negative charges are typically less likely to cross the membrane because of electrostatic forces. Nevertheless, studies have indicated that cellular membrane ionic imbalances may allow these negatively charged particles to penetrate directly [123]. Our prior research has evidenced that nanoparticles from diesel exhaust can creep through the BBB [31,48,54]. Nanoplastics with a positive charge, however, show a heightened capacity to infiltrate the BBB and become localized within cells [124]. Negatively charged polystyrene particles measuring 50 nm have been shown to cross the BBB by impacting tight junctions [125]. Furthermore, these negatively charged nanoplastics are more inclined to settle in rodent brains than their positively charged counterparts of identical size [126]. Conversely, positively charged polystyrene particles, ranging from 20–100 nm, are prone to increasing the permeability of the BBB [127]. This increase is partly due to potential membrane damage inflicted by structural disruption [128]. While there is evidence that nanoplastics permeating the BBB may lead to neurodegenerative changes, conclusive data remains elusive [47]. It should be noted that the literature on polystyrene nanoparticles surpasses that of other plastic varieties in terms of extent and depth.

11. Conclusions

Despite the widespread presence of micro- and nanoplastics in the environment, information on their absorption and toxicity remains limited. Research shows these particles can enter various organisms, including humans, fish, and mammals, through different exposure pathways. There's a significant lack of knowledge about the neurotoxic potential of these plastics. However, studies indicate that they might induce oxidative stress, inhibit the activity of AChE, impact neurotransmitter levels, and alter behavior in some species. It's still unclear if these effects relate to neurodevelopmental or neurodegenerative disorders in humans, unlike metal nanoparticles. Most experimental exposures to date don't mimic real human exposure situations, as they occur over short periods with high doses. In contrast, humans are exposed chronically to lower levels. Moreover, many studies use particle types and shapes that are not typical of environmental conditions. There's also a significant gap in systematically comparing various particle types, shapes, sizes, and concentrations. Most research so far has concentrated on aquatic species. To thoroughly understand the neurotoxin and exposure risks from micro- and nanoplastics, several actions are necessary:

1. Improved Monitoring: A better assessment of exposure levels for humans is needed, focusing on different exposure routes like inhalation, ingestion, and retrograde transport after nasal exposure, along with particle characteristics.

2. Focused Assessments: Research should investigate absorption through the lungs, nasal epithelium, or gut, potential crossing into the bloodstream, blood-brain barrier penetration, and organ accumulation, including the brain. It must determine direct transfer to the brain via nerve endings or indirect bloodstream transport, helping to identify the most dangerous particles for human health and the most vital exposure reduction measures.

3. Enhanced Risk Identification: Exposure time and particle dose standardization should incorporate dose-response curves, considering particle weight and number. Research should utilize various particle types, sizes, shapes, and surface charges, preferably those prevalent in the environment. For realistic assessments, aged and contaminated particles should be studied alongside virgin manufactured particles despite the complex toxicity.

4. Diversified Species Use: It's crucial to include different species, particularly mammals, given the variability in exposure routes. Laboratory assays can significantly aid hazard identification, increasing throughput, reducing costs, and providing mechanistic insights. However, the focus should be on subtle, functional effects beyond overt (neuro)toxic endpoints, as such effects may occur only at unrealistic exposure levels. Ultimately, irrespective of the findings from these hazard and risk evaluations of nanoplastics, measures should be implemented to minimize their further contamination and release into the environment.

Acknowledgments

We thank Dr. Ehsanifar Research Lab. Tehran, Iran.

Author Contributions

All the authors contributed to writing, reviewing and editing the manuscript.

Funding

This review received no external funding and was initiated and funded by Dr. Ehsanifar Research Lab, Tehran, Iran.

Competing Interests

The authors declare that they have no competing interests.

References

  1. Lebreton L, Andrady A. Future scenarios of global plastic waste generation and disposal. Palgrave Commun. 2019; 5: 6. [CrossRef]
  2. Li Y, Liu Z, Yang Y, Jiang Q, Wu D, Huang Y, et al. Effects of nanoplastics on energy metabolism in the oriental river prawn (Macrobrachium nipponense). Environ Pollut. 2021; 268: 115890. [CrossRef]
  3. Dris R, Gasperi J, Mirande C, Mandin C, Guerrouache M, Langlois V, et al. A first overview of textile fibers, including microplastics, in indoor and outdoor environments. Environ Pollut. 2017; 221: 453-458. [CrossRef]
  4. North EJ, Halden RU. Plastics and environmental health: The road ahead. Rev Environ Health. 2013; 28: 1-8. [CrossRef]
  5. Jambeck JR, Geyer R, Wilcox C, Siegler TR, Perryman M, Andrady A, et al. Plastic waste inputs from land into the ocean. Science. 2015; 347: 768-771. [CrossRef]
  6. Boucher J, Billard G. The challenges of measuring plastic pollution [Internet]. Paris, France: Field Actions Science Reports; 2019. Available from: https://journals.openedition.org/factsreports/5319.
  7. Gu L, Ozbakkaloglu T. Use of recycled plastics in concrete: A critical review. Waste Manage. 2016; 51: 19-42. [CrossRef]
  8. Chamas A, Moon H, Zheng J, Qiu Y, Tabassum T, Jang JH, et al. Degradation rates of plastics in the environment. ACS Sustain Chem Eng. 2020; 8: 3494-3511. [CrossRef]
  9. Zhu F, Zhu C, Wang C, Gu C. Occurrence and ecological impacts of microplastics in soil systems: A review. Bull Environ Contam Toxicol. 2019; 102: 741-749. [CrossRef]
  10. Bajt O. From plastics to microplastics and organisms. FEBS Open Bio. 2021; 11: 954-966. [CrossRef]
  11. Yuan J, Ma J, Sun Y, Zhou T, Zhao Y, Yu F. Microbial degradation and other environmental aspects of microplastics/plastics. Sci Total Environ. 2020; 715: 136968. [CrossRef]
  12. Hirt N, Body-Malapel M. Immunotoxicity and intestinal effects of nano-and microplastics: A review of the literature. Part Fibre Toxicol. 2020; 17: 57. [CrossRef]
  13. Mazurais D, Ernande B, Quazuguel P, Severe A, Huelvan C, Madec L, et al. Evaluation of the impact of polyethylene microbeads ingestion in European sea bass (Dicentrarchus labrax) larvae. Mar Environ Res. 2015; 112: 78-85. [CrossRef]
  14. Hanke G, Galgani F, Werner S, Oosterbaan L, Nilsson P, Fleet D, et al. Guidance on monitoring of Marine Litter in European seas: A guidance document within the common implementation strategy for the marine strategy framework directive. Luxembourg: European Commission, Joint Research Centre; 2013. [CrossRef]
  15. Costa JP, Duarte AC, Rocha-Santos TA. Microplastics-occurrence, fate and behaviour in the environment. Compr Anal Chem. 2017; 75: 1-24. [CrossRef]
  16. Horton AA, Walton A, Spurgeon DJ, Lahive E, Svendsen C. Microplastics in freshwater and terrestrial environments: Evaluating the current understanding to identify the knowledge gaps and future research priorities. Sci Total Environ. 2017; 586: 127-141. [CrossRef]
  17. Liu Z, Li Y, Pérez E, Jiang Q, Chen Q, Jiao Y, et al. Polystyrene nanoplastic induces oxidative stress, immune defense, and glycometabolism change in Daphnia pulex: Application of transcriptome profiling in risk assessment of nanoplastics. J Hazard Mater. 2021; 402: 123778. [CrossRef]
  18. Wang L, Wu WM, Bolan NS, Tsang DC, Li Y, Qin M, et al. Environmental fate, toxicity and risk management strategies of nanoplastics in the environment: Current status and future perspectives. J Hazard Mater. 2021; 401: 123415. [CrossRef]
  19. Sun H, Jiao R, Wang D. The difference of aggregation mechanism between microplastics and nanoplastics: Role of Brownian motion and structural layer force. Environ Pollut. 2021; 268: 115942. [CrossRef]
  20. Stojkovic M, Stojkovic P, Stankovic KM. Human pluripotent stem cells-unique tools to decipher the effects of environmental and intracellular plastic pollution on human health. Environ Pollut. 2021; 269: 116144. [CrossRef]
  21. Karthik R, Robin RS, Purvaja R, Ganguly D, Anandavelu I, Raghuraman R, et al. Microplastics along the beaches of southeast coast of India. Sci Total Environ. 2018; 645: 1388-1399. [CrossRef]
  22. Sangkham S, Faikhaw O, Munkong N, Sakunkoo P, Arunlertaree C, Chavali M, et al. A review on microplastics and nanoplastics in the environment: Their occurrence, exposure routes, toxic studies, and potential effects on human health. Mar Pollut Bull. 2022; 181: 113832. [CrossRef]
  23. Roman C, Mahé P, Latchere O, Catrouillet C, Gigault J, Métais I, et al. Effect of size continuum from nanoplastics to microplastics on marine mussel Mytilus edulis: Comparison in vitro/in vivo exposure scenarios. Comp Biochem Physiol C Toxicol Pharmacol. 2023; 264: 109512. [CrossRef]
  24. Rubio L, Marcos R, Hernández A. Potential adverse health effects of ingested micro-and nanoplastics on humans. Lessons learned from in vivo and in vitro mammalian models. J Toxicol Environ Health B. 2020; 23: 51-68. [CrossRef]
  25. Qiao J, Chen R, Wang M, Bai R, Cui X, Liu Y, et al. Perturbation of gut microbiota plays an important role in micro/nanoplastics-induced gut barrier dysfunction. Nanoscale. 2021; 13: 8806-8816. [CrossRef]
  26. Waring RH, Harris RM, Mitchell SC. Plastic contamination of the food chain: A threat to human health? Maturitas. 2018; 115: 64-68. [CrossRef]
  27. Toussaint B, Raffael B, Angers-Loustau A, Gilliland D, Kestens V, Petrillo M, et al. Review of micro-and nanoplastic contamination in the food chain. Food Addit Contam Part A. 2019; 36: 639-673. [CrossRef]
  28. Prata JC. Airborne microplastics: Consequences to human health? Environ Pollut. 2018; 234: 115-126. [CrossRef]
  29. Jani P, Halbert GW, Langridge J, Florence AT. Nanoparticle uptake by the rat gastrointestinal mucosa: Quantitation and particle size dependency. J Pharm Pharmacol. 1990; 42: 821-826. [CrossRef]
  30. Stock V, Böhmert L, Lisicki E, Block R, Cara-Carmona J, Pack LK, et al. Uptake and effects of orally ingested polystyrene microplastic particles in vitro and in vivo. Arch Toxikol. 2019; 93: 1817-1833. [CrossRef]
  31. Ehsanifar M, Montazeri Z, Zavareh MS, Rafati M, Wang J. Cognitive impairment, depressive-like behaviors and hippocampal microglia activation following exposure to air pollution nanoparticles. Environ Sci Pollut Res. 2023; 30: 23527-23537. [CrossRef]
  32. Ehsanifar M. Airborne aerosols particles and COVID-19 transition. Environ Res. 2021; 200: 111752. [CrossRef]
  33. Pauly JL, Stegmeier SJ, Allaart HA, Cheney RT, Zhang PJ, Mayer AG, et al. Inhaled cellulosic and plastic fibers found in human lung tissue. Cancer Epidemiol Biomarkers Prev. 1998; 7: 419-428.
  34. Schmidt C, Lautenschlaeger C, Collnot EM, Schumann M, Bojarski C, Schulzke JD, et al. Nano-and microscaled particles for drug targeting to inflamed intestinal mucosa-A first in vivo study in human patients. J Control Release. 2013; 165: 139-145. [CrossRef]
  35. Vethaak AD, Leslie HA. Plastic debris is a human health issue. Environ Sci Technol. 2016; 50: 6825-6826. [CrossRef]
  36. Lehner R, Weder C, Petri-Fink A, Rothen-Rutishauser B. Emergence of nanoplastic in the environment and possible impact on human health. Environ Sci Technol. 2019; 53: 1748-1765. [CrossRef]
  37. Feng Y, Tu C, Li R, Wu D, Yang J, Xia Y, et al. A systematic review of the impacts of exposure to micro-and nano-plastics on human tissue accumulation and health. Eco Environ Health. 2023; 2: 195-207. [CrossRef]
  38. Paing YM, Eom Y, Song GB, Kim B, Choi MG, Hong S, et al. Neurotoxic effects of polystyrene nanoplastics on memory and microglial activation: Insights from in vivo and in vitro studies. Sci Total Environ. 2024; 924: 171681. [CrossRef]
  39. Monikh FA, Lehtonen Š, Kekäläinen J, Karkossa I, Auriola S, Schubert K, et al. Biotransformation of nanoplastics in human plasma and their permeation through a model in vitro blood-brain barrier: An in-depth quantitative analysis. Nano Today. 2024; 59: 102466. [CrossRef]
  40. Panizzolo M, Martins VH, Ghelli F, Squillacioti G, Bellisario V, Garzaro G, et al. Biomarkers of oxidative stress, inflammation, and genotoxicity to assess exposure to micro-and nanoplastics. A literature review. Ecotoxicol Environ Saf. 2023; 267: 115645. [CrossRef]
  41. Xu D, Ma Y, Han X, Chen Y. Systematic toxicity evaluation of polystyrene nanoplastics on mice and molecular mechanism investigation about their internalization into Caco-2 cells. J Hazard Mater. 2021; 417: 126092. [CrossRef]
  42. Deng Y, Zhang Y, Lemos B, Ren H. Tissue accumulation of microplastics in mice and biomarker responses suggest widespread health risks of exposure. Sci Rep. 2017; 7: 46687. [CrossRef]
  43. MohanKumar SM, Campbell A, Block M, Veronesi B. Particulate matter, oxidative stress and neurotoxicity. Neurotoxicology. 2008; 29: 479-488. [CrossRef]
  44. Barboza LG, Vieira LR, Guilhermino L. Single and combined effects of microplastics and mercury on juveniles of the European seabass (Dicentrarchus labrax): Changes in behavioural responses and reduction of swimming velocity and resistance time. Environ Pollut. 2018; 236: 1014-1019. [CrossRef]
  45. Barboza LG, Cózar A, Gimenez BC, Barros TL, Kershaw PJ, Guilhermino L. Macroplastics pollution in the marine environment. In: World seas: An environmental evaluation. 2nd ed. Cambridge, MA: Academic Press; 2019. pp. 305-328. [CrossRef]
  46. O'Donovan S, Mestre NC, Abel S, Fonseca TG, Carteny CC, Cormier B, et al. Ecotoxicological effects of chemical contaminants adsorbed to microplastics in the clam Scrobicularia plana. Front Mar Sci. 2018; 5: 143. [CrossRef]
  47. Prüst M, Meijer J, Westerink RH. The plastic brain: Neurotoxicity of micro-and nanoplastics. Part Fibre Toxicol. 2020; 17: 24. [CrossRef]
  48. Ehsanifar M, Tameh AA, Farzadkia M, Kalantari RR, Zavareh MS, Nikzaad H, et al. Exposure to nanoscale diesel exhaust particles: Oxidative stress, neuroinflammation, anxiety and depression on adult male mice. Ecotoxicol Environ Saf. 2019; 168: 338-347. [CrossRef]
  49. Ehsanifar M, Rajati R, Gholami A, Reiss JP. Mold and mycotoxin exposure and brain disorders. J Integr Neurosci. 2023; 22: 137. [CrossRef]
  50. Ehsanifar M, Montazeri Z, Taheri MA, Rafati M, Behjati M, Karimian M. Hippocampal inflammation and oxidative stress following exposure to diesel exhaust nanoparticles in male and female mice. Neurochem Int. 2021; 145: 104989. [CrossRef]
  51. Ehsanifar M, Jafari AJ, Montazeri Z, Kalantari RR, Gholami M, Ashtarinezhad A. Learning and memory disorders related to hippocampal inflammation following exposure to air pollution. J Environ Health Sci Eng. 2021; 19: 261-272. [CrossRef]
  52. Khan FA, Almohazey D, Alomari M, Almofty SA. Impact of nanoparticles on neuron biology: Current research trends. Int J Nanomed. 2018; 13: 2767-2776. [CrossRef]
  53. Teleanu DM, Chircov C, Grumezescu AM, Teleanu RI. Neurotoxicity of nanomaterials: An up-to-date overview. Nanomaterials. 2019; 9: 96. [CrossRef]
  54. Ehsanifar M, Yavari Z, Rafati M. Exposure to urban air pollution particulate matter: Neurobehavioral alteration and hippocampal inflammation. Environ Sci Pollut Res. 2022; 29: 50856-50866. [CrossRef]
  55. Oszlánczi G, Vezér T, Sárközi L, Horváth E, Szabó A, Horváth E, et al. Metal deposition and functional neurotoxicity in rats after 3-6 weeks nasal exposure by two physicochemical forms of manganese. Environ Toxicol Pharmacol. 2010; 30: 121-126. [CrossRef]
  56. Ehsanifar M, Montazeri Z, Rafati M. Alzheimer’s disease-like neuropathology following exposure to ambient noise. J Biomed Res Environ Sci. 2021; 2: 1159-1162. [CrossRef]
  57. Ehsanifar M, Jafari AJ, Nikzad H, Zavareh MS, Atlasi MA, Mohammadi H, et al. Prenatal exposure to diesel exhaust particles causes anxiety, spatial memory disorders with alters expression of hippocampal pro-inflammatory cytokines and NMDA receptor subunits in adult male mice offspring. Ecotoxicol Environ Saf. 2019; 176: 34-41. [CrossRef]
  58. Fernández-Bertólez N, Costa C, Bessa MJ, Park M, Carriere M, Dussert F, et al. Assessment of oxidative damage induced by iron oxide nanoparticles on different nervous system cells. Mutat Res Genet Toxicol Environ Mutagen. 2019; 845: 402989. [CrossRef]
  59. Wu J, Ding T, Sun J. Neurotoxic potential of iron oxide nanoparticles in the rat brain striatum and hippocampus. Neurotoxicology. 2013; 34: 243-253. [CrossRef]
  60. Haase A, Rott S, Mantion A, Graf P, Plendl J, Thünemann AF, et al. Effects of silver nanoparticles on primary mixed neural cell cultures: Uptake, oxidative stress and acute calcium responses. Toxicol Sci. 2012; 126: 457-468. [CrossRef]
  61. Liu Y, Guan W, Ren G, Yang Z. The possible mechanism of silver nanoparticle impact on hippocampal synaptic plasticity and spatial cognition in rats. Toxicol Lett. 2012; 209: 227-231. [CrossRef]
  62. Niska K, Santos-Martinez MJ, Radomski MW, Inkielewicz-Stepniak I. CuO nanoparticles induce apoptosis by impairing the antioxidant defense and detoxification systems in the mouse hippocampal HT22 cell line: Protective effect of crocetin. Toxicol In Vitro. 2015; 29: 663-671. [CrossRef]
  63. An L, Liu S, Yang Z, Zhang T. Cognitive impairment in rats induced by nano-CuO and its possible mechanisms. Toxicol Lett. 2012; 213: 220-227. [CrossRef]
  64. Bouwmeester H, Hollman PC, Peters RJ. Potential health impact of environmentally released micro-and nanoplastics in the human food production chain: Experiences from nanotoxicology. Environ Sci Technol. 2015; 49: 8932-8947. [CrossRef]
  65. Luyts K, Napierska D, Nemery B, Hoet PH. How physico-chemical characteristics of nanoparticles cause their toxicity: Complex and unresolved interrelations. Environ Sci Process Impacts. 2013; 15: 23-38. [CrossRef]
  66. Truong L, Saili KS, Miller JM, Hutchison JE, Tanguay RL. Persistent adult zebrafish behavioral deficits results from acute embryonic exposure to gold nanoparticles. Comp Biochem Physiol C Toxicol Pharmacol. 2012; 155: 269-274. [CrossRef]
  67. Dedeh A, Ciutat A, Treguer-Delapierre M, Bourdineaud JP. Impact of gold nanoparticles on zebrafish exposed to a spiked sediment. Nanotoxicology. 2015; 9: 71-80. [CrossRef]
  68. Ferreira GK, Cardoso E, Vuolo FS, Galant LS, Michels M, Goncalves CL, et al. Effect of acute and long-term administration of gold nanoparticles on biochemical parameters in rat brain. Mater Sci Eng C. 2017; 79: 748-755. [CrossRef]
  69. Miranda RR, Damaso da Silveira AL, De Jesus IP, Grötzner SR, Voigt CL, Campos SX, et al. Effects of realistic concentrations of TiO2 and ZnO nanoparticles in prochilodus lineatus juvenile fish. Environ Sci Pollut Res. 2016; 23: 5179-5188. [CrossRef]
  70. Sheng L, Wang L, Su M, Zhao X, Hu R, Yu X, et al. Mechanism of TiO2 nanoparticle‐induced neurotoxicity in zebrafish (Danio rerio). Environ Toxicol. 2016; 31: 163-175. [CrossRef]
  71. Hu Q, Guo F, Zhao F, Fu Z. Effects of titanium dioxide nanoparticles exposure on parkinsonism in zebrafish larvae and PC12. Chemosphere. 2017; 173: 373-379. [CrossRef]
  72. Carmo TL, Siqueira PR, Azevedo VC, Tavares D, Pesenti EC, Cestari MM, et al. Overview of the toxic effects of titanium dioxide nanoparticles in blood, liver, muscles, and brain of a neotropical detritivorous fish. Environ Toxicol. 2019; 34: 457-468. [CrossRef]
  73. Shrivastava R, Raza S, Yadav A, Kushwaha P, Flora SJ. Effects of sub-acute exposure to TiO2, ZnO and Al2O3 nanoparticles on oxidative stress and histological changes in mouse liver and brain. Drug Chem Toxicol. 2014; 37: 336-347. [CrossRef]
  74. Grissa I, Guezguez S, Ezzi L, Chakroun S, Sallem A, Kerkeni E, et al. The effect of titanium dioxide nanoparticles on neuroinflammation response in rat brain. Environ Sci Pollut Res. 2016; 23: 20205-20513. [CrossRef]
  75. Hu R, Gong X, Duan Y, Li N, Che Y, Cui Y, et al. Neurotoxicological effects and the impairment of spatial recognition memory in mice caused by exposure to TiO2 nanoparticles. Biomaterials. 2010; 31: 8043-8050. [CrossRef]
  76. Ze X, Su M, Zhao X, Jiang H, Hong J, Yu X, et al. TiO2 nanoparticle‐induced neurotoxicity may be involved in dysfunction of glutamate metabolism and its receptor expression in mice. Environ Toxicol. 2016; 31: 655-662. [CrossRef]
  77. Horváth T, Vezér T, Kozma G, Papp A. Functional neurotoxicity and tissue metal levels in rats exposed subacutely to titanium dioxide nanoparticles via the airways. Ideggyogy Sz. 2018; 71: 35-42. [CrossRef]
  78. Ze Y, Sheng L, Zhao X, Ze X, Wang X, Zhou Q, et al. Neurotoxic characteristics of spatial recognition damage of the hippocampus in mice following subchronic peroral exposure to TiO2 nanoparticles. J Hazard Mater. 2014; 264: 219-229. [CrossRef]
  79. Long TC, Saleh N, Tilton RD, Lowry GV, Veronesi B. Titanium dioxide (P25) produces reactive oxygen species in immortalized brain microglia (BV2): Implications for nanoparticle neurotoxicity. Environ Sci Technol. 2006; 40: 4346-4352. [CrossRef]
  80. Coccini T, Grandi S, Lonati D, Locatelli C, De Simone U. Comparative cellular toxicity of titanium dioxide nanoparticles on human astrocyte and neuronal cells after acute and prolonged exposure. Neurotoxicology. 2015; 48: 77-89. [CrossRef]
  81. Erriquez J, Bolis V, Morel S, Fenoglio I, Fubini B, Quagliotto P, et al. Nanosized TiO2 is internalized by dorsal root ganglion cells and causes damage via apoptosis. Nanomedicine. 2015; 11: 1309-1319. [CrossRef]
  82. He Q, Zhou X, Liu Y, Gou W, Cui J, Li Z, et al. Titanium dioxide nanoparticles induce mouse hippocampal neuron apoptosis via oxidative stress-and calcium imbalance-mediated endoplasmic reticulum stress. Environ Toxicol Pharmacol. 2018; 63: 6-15. [CrossRef]
  83. Lei L, Liu M, Song Y, Lu S, Hu J, Cao C, et al. Polystyrene (nano) microplastics cause size-dependent neurotoxicity, oxidative damage and other adverse effects in Caenorhabditis elegans. Environ Sci Nano. 2018; 5: 2009-2020. [CrossRef]
  84. Guo M, Fang Y, Zhu J, Chen C, Zhang Z, Tian X, et al. Investigation of metabolic kinetics in different brain regions of awake rats using the [1H-13C]-NMR technique. J Pharm Biomed Anal. 2021; 204: 114240. [CrossRef]
  85. Chen Y, Liu X, Leng Y, Wang J. Defense responses in earthworms (Eisenia fetida) exposed to low-density polyethylene microplastics in soils. Ecotoxicol Environ Saf. 2020; 187: 109788. [CrossRef]
  86. Magni S, Gagné F, André C, Della Torre C, Auclair J, Hanana H, et al. Evaluation of uptake and chronic toxicity of virgin polystyrene microbeads in freshwater zebra mussel Dreissena polymorpha (Mollusca: Bivalvia). Sci Total Environ. 2018; 631: 778-788. [CrossRef]
  87. Ribeiro F, Garcia AR, Pereira BP, Fonseca M, Mestre NC, Fonseca TG, et al. Microplastics effects in Scrobicularia plana. Mar Pollut Bull. 2017; 122: 379-391. [CrossRef]
  88. Brandts I, Teles M, Gonçalves AP, Barreto A, Franco-Martinez L, Tvarijonaviciute A, et al. Effects of nanoplastics on Mytilus galloprovincialis after individual and combined exposure with carbamazepine. Sci Total Environ. 2018; 643: 775-784. [CrossRef]
  89. Avio CG, Gorbi S, Milan M, Benedetti M, Fattorini D, d'Errico G, et al. Pollutants bioavailability and toxicological risk from microplastics to marine mussels. Environ Pollut. 2015; 198: 211-222. [CrossRef]
  90. Guilhermino L, Vieira LR, Ribeiro D, Tavares AS, Cardoso V, Alves A, et al. Uptake and effects of the antimicrobial florfenicol, microplastics and their mixtures on freshwater exotic invasive bivalve Corbicula fluminea. Sci Total Environ. 2018; 622: 1131-1142. [CrossRef]
  91. Oliveira P, Barboza LG, Branco V, Figueiredo N, Carvalho C, Guilhermino L. Effects of microplastics and mercury in the freshwater bivalve corbicula fluminea (Müller, 1774): Filtration rate, biochemical biomarkers and mercury bioconcentration. Ecotoxicol Environ Saf. 2018; 164: 155-163. [CrossRef]
  92. Gambardella C, Morgana S, Ferrando S, Bramini M, Piazza V, Costa E, et al. Effects of polystyrene microbeads in marine planktonic crustaceans. Ecotoxicol Environ Saf. 2017; 145: 250-257. [CrossRef]
  93. Varó I, Perini A, Torreblanca A, Garcia Y, Bergami E, Vannuccini ML, et al. Time-dependent effects of polystyrene nanoparticles in brine shrimp artemia franciscana at physiological, biochemical and molecular levels. Sci Total Environ. 2019; 675: 570-580. [CrossRef]
  94. Rafiee M, Dargahi L, Eslami A, Beirami E, Jahangiri-Rad M, Sabour S, et al. Neurobehavioral assessment of rats exposed to pristine polystyrene nanoplastics upon oral exposure. Chemosphere. 2018; 193: 745-753. [CrossRef]
  95. Marsden P, Koelmans AA, Bourdon-Lacombe J, Gouin T, D'anglada L, Cunliffe D, et al. Microplastics in drinking water. Geneva, Switzerland: World Health Organization; 2019.
  96. Ding J, Zhang S, Razanajatovo RM, Zou H, Zhu W. Accumulation, tissue distribution, and biochemical effects of polystyrene microplastics in the freshwater fish red tilapia (Oreochromis niloticus). Environ Pollut. 2018; 238: 1-9. [CrossRef]
  97. Zhang S, Ding J, Razanajatovo RM, Jiang H, Zou H, Zhu W. Interactive effects of polystyrene microplastics and roxithromycin on bioaccumulation and biochemical status in the freshwater fish red tilapia (Oreochromis niloticus). Sci Total Environ. 2019; 648: 1431-1439. [CrossRef]
  98. Ferreira P, Fonte E, Soares ME, Carvalho F, Guilhermino L. Effects of multi-stressors on juveniles of the marine fish Pomatoschistus microps: Gold nanoparticles, microplastics and temperature. Aquat Toxicol. 2016; 170: 89-103. [CrossRef]
  99. Fonte E, Ferreira P, Guilhermino L. Temperature rise and microplastics interact with the toxicity of the antibiotic cefalexin to juveniles of the common goby (Pomatoschistus microps): Post-exposure predatory behaviour, acetylcholinesterase activity and lipid peroxidation. Aquat Toxicol. 2016; 180: 173-185. [CrossRef]
  100. Browne MA, Dissanayake A, Galloway TS, Lowe DM, Thompson RC. Ingested microscopic plastic translocates to the circulatory system of the mussel, Mytilus edulis (L.). Environ Sci Technol. 2008; 42: 5026-5031. [CrossRef]
  101. Mattsson K, Johnson EV, Malmendal A, Linse S, Hansson LA, Cedervall T. Brain damage and behavioural disorders in fish induced by plastic nanoparticles delivered through the food chain. Sci Rep. 2017; 7: 11452. [CrossRef]
  102. Murali K, Li Y, Demeter K, Környei Z, Madarász E. Uptake and bio-reactivity of polystyrene nanoparticles is affected by surface modifications, ageing and LPS adsorption: In vitro studies on neural tissue cells. Nanoscale. 2015; 7: 4199-4210. [CrossRef]
  103. Patil S, Sandberg A, Heckert E, Self W, Seal S. Protein adsorption and cellular uptake of cerium oxide nanoparticles as a function of zeta potential. Biomaterials. 2007; 28: 4600-4607. [CrossRef]
  104. Fröhlich E. The role of surface charge in cellular uptake and cytotoxicity of medical nanoparticles. Int J Nanomed. 2012; 7: 5577-5591. [CrossRef]
  105. Koelmans AA, Bakir A, Burton GA, Janssen CR. Microplastic as a vector for chemicals in the aquatic environment: Critical review and model-supported reinterpretation of empirical studies. Environ Sci Technol. 2016; 50: 3315-3326. [CrossRef]
  106. Viršek MK, Lovšin MN, Koren Š, Kržan A, Peterlin M. Microplastics as a vector for the transport of the bacterial fish pathogen species Aeromonas salmonicida. Mar Pollut Bull. 2017; 125: 301-309. [CrossRef]
  107. Xie J, Sun Y, Ma Y, Wu D, Zhang Z. Blood-brain barrier damage accelerates the accumulation of micro-and nanoplastics in the human central nervous system. J Hazard Mater. 2024; 480: 136028. [CrossRef]
  108. Canton I, Battaglia G. Endocytosis at the nanoscale. Chem Soc Rev. 2012; 41: 2718-2739. [CrossRef]
  109. Liu S, Wu X, Gu W, Yu J, Wu B. Influence of the digestive process on intestinal toxicity of polystyrene microplastics as determined by in vitro Caco-2 models. Chemosphere. 2020; 256: 127204. [CrossRef]
  110. Brown TD, Habibi N, Wu D, Lahann J, Mitragotri S. Effect of nanoparticle composition, size, shape, and stiffness on penetration across the blood-brain barrier. ACS Biomater Sci Eng. 2020; 6: 4916-4928. [CrossRef]
  111. Mazumdar S, Chitkara D, Mittal A. Exploration and insights into the cellular internalization and intracellular fate of amphiphilic polymeric nanocarriers. Acta Pharm Sin B. 2021; 11: 903-924. [CrossRef]
  112. Monikh FA, Vijver MG, Kortet R, Lynch I, Peijnenburg WJ. Emerging investigator series: Perspectives on toxicokinetics of nanoscale plastic debris in organisms. Environ Sci Nano. 2022; 9: 1566-1577. [CrossRef]
  113. Zhou R, Zhou D, Yang S, Shi Z, Pan H, Jin Q, et al. Neurotoxicity of polystyrene nanoplastics with different particle sizes at environment-related concentrations on early zebrafish embryos. Sci Total Environ. 2023; 872: 162096. [CrossRef]
  114. Yin K, Wang Y, Zhao H, Wang D, Guo M, Mu M, et al. A comparative review of microplastics and nanoplastics: Toxicity hazards on digestive, reproductive and nervous system. Sci Total Environ. 2021; 774: 145758. [CrossRef]
  115. Liu D, Lin B, Shao W, Zhu Z, Ji T, Yang C. In vitro and in vivo studies on the transport of PEGylated silica nanoparticles across the blood-brain barrier. ACS Appl Mater Interfaces. 2014; 6: 2131-2136. [CrossRef]
  116. Kopatz V, Wen K, Kovács T, Keimowitz AS, Pichler V, Widder J, et al. Micro-and nanoplastics breach the blood-brain barrier (BBB): Biomolecular corona’s role revealed. Nanomaterials. 2023; 13: 1404. [CrossRef]
  117. Da Silva-Candal A, Brown T, Krishnan V, Lopez-Loureiro I, Ávila-Gómez P, Pusuluri A, et al. Shape effect in active targeting of nanoparticles to inflamed cerebral endothelium under static and flow conditions. J Control Release. 2019; 309: 94-105. [CrossRef]
  118. Kolhar P, Anselmo AC, Gupta V, Pant K, Prabhakarpandian B, Ruoslahti E, et al. Using shape effects to target antibody-coated nanoparticles to lung and brain endothelium. Proc Natl Acad Sci. 2013; 110: 10753-10758. [CrossRef]
  119. Salatin S, Maleki Dizaj S, Yari Khosroushahi A. Effect of the surface modification, size, and shape on cellular uptake of nanoparticles. Cell Biol Int. 2015; 39: 881-890. [CrossRef]
  120. Urani C, Barbieri R, Alloisio S, Tesauro M. From the environment to molecular interactions of nanoplastics: Unraveling the neurotoxic impacts and the implications in neurodegenerative processes. Appl Sci. 2024; 14: 7280. [CrossRef]
  121. Monikh FA, Durão M, Kipriianov PV, Huuskonen H, Kekäläinen J, Uusi-Heikkilä S, et al. Chemical composition and particle size influence the toxicity of nanoscale plastic debris and their co-occurring benzo (α) pyrene in the model aquatic organisms daphnia magna and danio rerio. NanoImpact. 2022; 25: 100382. [CrossRef]
  122. Santoro A, Marino M, Vandenberg LN, Szychlinska MA, Lamparelli EP, Scalia F, et al. PLASTAMINATION: Outcomes on the central nervous system and reproduction. Curr Neuropharmacol. 2024; 22: 1870-1898. [CrossRef]
  123. Gan AJ, Chia KF, Lim CL, Tan BK, Wong SF, Chye SM, et al. Neurotoxicity of nanoplastics: A review. F1000Research. 2024; 13: 793. [CrossRef]
  124. Chirio D, Gallarate M, Peira E, Battaglia L, Muntoni E, Riganti C, et al. Positive-charged solid lipid nanoparticles as paclitaxel drug delivery system in glioblastoma treatment. Eur J Pharm Biopharm. 2014; 88: 746-758. [CrossRef]
  125. Shan S, Zhang Y, Zhao H, Zeng T, Zhao X. Polystyrene nanoplastics penetrate across the blood-brain barrier and induce activation of microglia in the brain of mice. Chemosphere. 2022; 298: 134261. [CrossRef]
  126. Grodzicki W, Dziendzikowska K, Gromadzka-Ostrowska J, Kruszewski M. Nanoplastic impact on the gut-brain axis: Current knowledge and future directions. Int J Mol Sci. 2021; 22: 12795. [CrossRef]
  127. Zhang L, Fan J, Li G, Yin Z, Fu BM. Transcellular model for neutral and charged nanoparticles across an in vitro blood-brain barrier. Cardiovasc Eng Technol. 2020; 11: 607-620. [CrossRef]
  128. Fröhlich E, Meindl C, Roblegg E, Ebner B, Absenger M, Pieber TR. Action of polystyrene nanoparticles of different sizes on lysosomal function and integrity. Part Fibre Toxicol. 2012; 9: 26. [CrossRef]
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