A Comprehensive Review of Arsenic-Induced Neurotoxicity: Exploring the Role of Glial Cell Pathways and Mechanisms.

The review aims to examine the neurotoxic effects of arsenic, particularly exploring the roles of glial cells-astrocytes, microglia, and oligodendrocytes, amid its widespread environmental contamination and impact on cognitive impairments. It highlights the role of altered neurotrophin and growth factor signaling in disrupting neuronal health and cognitive performance. It elucidates the intricate interactions between oxidative stress, DNA damage, neurotransmitter disruption, and cellular signaling alterations, underscoring the vital importance of the glial cells. These cells are crucial for preserving neural health and responding to environmental toxins, and arsenic disrupts their functions, resulting in decreased antioxidative responses, induction of inflammatory pathways, and subsequent neuronal dysfunction. The brain's cytotoxic impact arises from a complex network of cellular responses, with pathways such as MAPK, transcription factor and autophagy signaling to play critical roles in mediating these dysregulated inflammation and oxidative stress mechanisms. The detailed exploration into specific impacts of arsenic on glial cell morphology, activation, and mitochondrial functions illuminates the cascade of neuroinflammatory and neurodegenerative changes that may be triggered upon arsenic exposure. The review recommends a multidisciplinary research approach by emphasizing the significance of the brain's microenvironment, methylation processes, and the enzyme AS3MT in arsenic neurotoxicity. It calls for converging environmental science, neurobiology, and toxicology to develop targeted interventions for preventing and mitigating arsenic's neurotoxic effects. This in-depth exploration into glial cell dynamics aims to advance public health and neurotoxicology research, striving to devise strategies that reduce the cognitive and neurodegenerative damage caused by arsenic, thereby enhancing global health outcomes.