## 3 Neurotoxicity of Micro and Nano-Plastics in Fish
In zebrafish, the _gfap_ gene and the corresponding protein are highly conserved and exhibit functions similar to those of mammals [86]. Moreover, the up regulation of _gfap_ is an indicator of neurotoxicity, also observed in mammals [86,87]. The use of _gfap_'s upregulation in neurotoxicity screenings is now accepted, and its use by the US Environmental Protection Agency (EPA) has been recommended [88]. Instead, the up regulation of _gfap_ and _a1-tubulin_ in the central nervous system promotes an increase in the expression of zfrho and zfblue and this alteration may be a side effect of neurotoxicity [87]. Zebrafish larvae exposed to nanoplastics showed more severe hypoactivity phenomena when co-exposed to NPPs E EE2 due to oxidative damage [60]. In treatments with MPP and MPP + EE2, the up-regulation of sight-related genes such as opsin which is expelled by photoreceptor cells of the retina [89] has been observed [60]. Upregulation of the opsin gene cannot indicate alterations in movement [90]. In _Clarias gariepinus_ the effects of PVC microparticles, considering a battery of biomarkers of oxidative stress (superoxide dismutase, catalase, glutathione peroxidase), neurotoxicity (acetylcholinesteraseerase) and lipid peroxidation, have been evaluated [53]. It has been shown that in the presence of PVC the activity of GPx, Sod, Cat, and AchE is inhibited while the levels of LPO have increased, all progressively with time [53]. Specimens of red tilapia were exposed to polystyrene particles of three different sizes (0.3, 5 and 70-90 \(\upmu\)m) to evaluate their accumulation, oxidative stress, p450 enzyme activity, metabolic changes, and neurotoxicity. It was shown that only the 5 \(\upmu\)m polystyrene microplastics significantly inhibited the activity of acetyl cholinesterase in the brain. In this species, in treatments with PS-N and MPs (0.3, 5 and 70-90 \(\upmu\)m) a decrease in the activity of the enzyme acetylcholinesteraseinase in the brain has been observed [45], confirming previous studies in the same species [40] and in _P. microps_[91], as well as in zebrafish larva [60]. It has been shown that plastic materials are capable of conveying pollutants to the body's tissues [60,92]. Although some authors give little importance to this vector function [93,94,95,96], it is known that the toxicity of plastics and their interaction with others pollutants can affect the bioavailability and toxicity of these pollutants for the biota [92]. Plastics have shown the ability to absorb various pollutants (IPA, PCB, HCH) [97]. Furthermore, all additives added to plastics must be taken into consideration: plasticizers, flame retardants and antimicrobials whose toxicity can be altered by co-exposure with the transported toxicants [98,99]. In epoxy resins and polycarbonate plastics, the most used additive is bisphenol A (BPA). This additive can be released from plastic materials into the aquatic environment and can reach a concentration of 4 \(\upmu\)g/L [98,100,101]. While for years it has been considered a cause of obesity and disorders of the immune and endocrine systems [102,103], [PERSON] et al. [104] highlighted the negative effects of BPA on the brain. The accumulation of BPA and NPPs in various zebrafish organs including the brain has been demonstrated [43,105]. [PERSON] et al. [106] evaluated the different expression of genes and proteins as biomarkers of neurotoxicity during the development of the zebrafish central nervous system. [PERSON] et al. [61] demonstrated that the co-exposure of NPPs and BPA not only leads to increased accumulation of BPA in zebrafish organs, but is responsible for neurotoxic effects on the central nervous and dopaminergic systems. Indeed, during co-exposure to NPPs and BPA, not only the upregulation of myelin and tubulin basic protein genes in the central nervous system and increased dopamine, but also upregulation of astrocyte-derived neurotrophic factor (MANF) expression in the midbrain and significant inhibition of acetyl cholinesteraseterase enzyme activity [61] were evident.