Arsenic Exposure Induces Cognitive Impairment in Mice with Increased Acetylcholinesterase Activity and Inflammation in the Cortex and Hippocampus: Implications for Alzheimer's Disease.

Abstract

Introduction: Arsenic, a metalloid, is well associated as a risk factor for the development and progression of neurodegenerative diseases, including Alzheimer's Disease (AD), which is characterized by impairment in cognition. However, specific effects of arsenic on Acetylcholinesterase (AChE) activity and inflammatory markers in different brain regions, as well as its impact on behaviour, are not yet fully understood.

Methods: Arsenic was administered (20 mg/kg by gavage for 4 weeks) to male and female mice, and its effects on behaviour were assessed by using the object recognition memory test and lightdark box test. AChE activity and neuronal Nitric Oxide (nNOS) were assessed by histoenzymology, and immunohistochemistry was employed for assessment of Glial Fibrillary Acidic Protein (GFAP).

Results: Both the behavioural tests showed significant impairment of learning and memory functions and development of psychiatric abnormalities in arsenic-fed mice. The histoenzymology and immunohistochemistry analysis of the cortex and hippocampus region of these arsenic-fed mice revealed the increment of AChE activity and inflammatory markers, viz. GFAP and nNOS.

Discussion: The observed increment in AChE activity in the cortex and hippocampus of arsenic-fed mice may contribute to the impairment of learning and memory functions, as well as to the development of psychiatric abnormalities. Furthermore, the enhancement of inflammatory processes in these brain regions may be either a consequence or a contributing factor to the elevated AChE activity, thus establishing a self-fuelling cycle of neuroinflammation and increased AChE activity.

Conclusion: Given the gender bias in neurodegenerative diseases, our findings indicate that arsenic exposure does not lead to significant differences in neuropathological and neurobehavioural outcomes between male and female mice. Moreover, current outcomes underscore the potential of arsenic to act as a neurotoxic agent in AD development.