Silent but Deadly: An Overview Unraveling the Neuropathological Actions of Mercury on the Central Nervous System

Mercury (Hg) is a ubiquitous heavy metal known for its neurotoxic effects, with its impact on the nervous system critically influenced by its chemical speciation. Its natural sources include volcanic activity, geological deposits, geothermal springs, and oceans. In contrast, human activities- such as industrial processes, gold mining, hazardous waste incineration, and fossil fuel combustion- further contribute to environmental Hg levels. Exposure to Hg, primarily through inhalation, ingestion, or skin contact, can result in significant neurological damage. Hg exists in various forms, with methylmercury (MeHg) being the most toxic, readily accumulating in brain tissue. In vitro and in vivo studies indicate that MeHg disrupts synaptic transmission, impairs neuronal signaling, alters cell structure, induces oxidative stress, triggers inflammatory responses, and causes both necrotic and apoptotic cell death. These disturbances can manifest as cognitive deficits, mood disorders, and motor dysfunction. Moreover, Hg's ability to cross the blood-brain barrier exacerbates its neurotoxic potential, leading to long-lasting effects even after exposure ceases. Given its socio-economic impacts, Hg contamination and the resulting exposure of humans and wildlife have prompted policies and regulations aimed at reducing emissions from human activities. In this context, this review summarizes the major sources and health impacts of Hg exposure, with a particular focus on the mechanisms of MeHg-induced neurotoxicity. We highlight evidence from experimental models that implicates oxidative stress, neuroinflammation, and cell death as central pathways underlying its harmful effects on the nervous system.