## 5 Neurodegenerative Diseases and Environmental Factors
The type of corona formed significantly influences the ability of NPs to breach the blood-brain barrier (BBB) and their overall toxicity. Molecular dynamics simulations using lipids 1,2-Dioleoyl-sn-glycero-3-phosphocholine as a model of the membrane and a representative of the BBB demonstrate that polystyrene (PS) plastic particles (5 nm) can traverse both the gastrointestinal barrier and the BBB swiftly, contingent on their specific surface coronas [8]. These findings are corroborated by in vivo mouse models, which indicate the presence of nanometric-sized PS particles in brain tissues as early as 2 h post-exposure. Size is another critical determinant influencing the capacity of plastic particles to penetrate the BBB, with only particles measuring 293 nm being absorbed by the gastrointestinal tract and capable of breaching the BBB in mice models exposed to a mixture of different sizes of MP and NP particles (9.55 um,1.14 um, 293 nm) [8]. Synthesized fluorescent PS-NPs (30-50 nm) can reach brain tissues of orally exposed mice [113], suggesting that the gut-brain connection is pivotal in oral exposure to plastic particles and brain damage caused by NPs. Recent advances [114, 115] using in vivo (mouse) and in vitro models (i.e., bEnd.3 endothelial cells from mouse brain tissue or hCMEC/D3 cells, recognized as a cell line for human BBB model) confirm the ability of PS-NPs to cross through the BBB and clarify the underlying mechanisms [115]. PS-NPs 50 nm in size, characterized by transmission electron microscopy and scanning electron microscopy, reduce the transendothelial electrical resistance by altering the expression of the scaffold protein zona occludens-1 (ZO-1), responsible for the actin cytoskeleton's connection to the transmembrane protein occludin, which preserves the integrity of the BBB. The molecular analyses further suggest that pathways of ferroptosis, iron-mediated cell death which adversely affects brain function (see, e.g., [116]), is related to BBB disruption [114]. The internalization of PS-NPs (100 nm) was evidenced in a neuronal model (mouse hippocampal neuronal cells, HT22), leading to decreased cell viability [117]. In addition, studies both in mice and in vitro demonstrate the ability of PS-NPs to accumulate and activate microglia cells, which in turn leads to neuronal damage [115]. Given the BBB's pivotal role in shielding the brain from harmful substances, its compromise can precipitate various neurological issues. Therefore, the short-term health ramifications of NPs warrant consideration, as their presence in the brain may precipitate cognitive impairment, neurological disorders, and neurotoxicity, ultimately impeding brain function [118]. Furthermore, the intestinal tract, beyond its role in digestion and nutrient absorption, serves as a crucial interface between the organism and the environment. It also facilitates communication with the CNS through the so called \"gut-brain axis\", a complex network where neuroendocrine and immunological signaling pathways, along with bidirectional neural mechanisms, interact, influenced by the gut microbiome, potentially impactingbrain damage and neuroinflammatory processes. These factors modulate various processes, including neuroinflammation, aberrant BBB permeability, microglial activation, immune system responses, and mitochondrial dysfunction, all of which are critical to the progression of brain-related pathologies [119, 120, 121]. Neurodegenerative processes may be initiated by the enteric nervous system, the vagus nerve, and the bloodstream through neuroactive compounds such as serotonin or dopamine, as well as cytokines [122]. These pathways' activation, demonstrated for ambient ultrafine particulate matter (UFPM) and the transfer of iron from UFPM into the brain, and for several metals transiting via olfactory receptor neurons from the nasal lumen to the olfactory bulb, could similarly be exploited by plastic particles [123, 124].