Developmental and lifelong exposure to mercury chloride exacerbates cognitive and motor decline in aged mice

Abstract

Aging is a multifactorial biological process characterized by the progressive decline of cellular, tissue, and organ functions, leading to increased vulnerability to neurodegenerative disorders. Among the proposed mechanisms, the oxidative stress theory of aging remains one of the most widely accepted, emphasizing the role of reactive oxygen species (ROS) accumulation, particularly in the central nervous system (CNS). Mercury is a persistent environmental pollutant known to induce oxidative damage, but its contribution to age-related neuronal decline remains poorly understood. Our aim of this study was to investigate whether chronic HgCl2 exposure exacerbates age-related decline in memory and locomotor functions in aged male mice. To this end, mice were divided into two groups: A control group, which received only tap water, and an HgCl2-exposed group, which received 40 ppm HgCl2 in their drinking water daily from gestation until 18 months of age. At the end of the exposure, mice were subjected to behavioral tests to assess memory and locomotor activity. Following these behavioral assessments, oxidative stress parameters and acetylcholinesterase (AChE) activity were measured in the hippocampus and cerebellum. Our results showed that HgCl2 impaired locomotor activity in the Open Field test (OF) and memory performance in the Y-maze and Novel Object Recognition (NOR) test. These deficits were accompanied by a significant increase in malondialdehyde (MDA) and acetylcholinesterase (AChE) activity in the hippocampus. Furthermore, mercury exposure led to an increase in MDA and a significant upregulation of catalase (CAT) and superoxide dismutase (SOD) activities in the cerebellum. These changes were also associated with a marked decrease in AChE activity within the same region. Overall, these findings suggest that lifelong mercury exposure accelerates neurobehavioral decline by exacerbating oxidative and cholinergic disturbances, providing insight into how early and sustained exposure to environmental toxicants may promote premature brain aging.