Mercury is a pervasive environmental neurotoxin with well-documented effects on the mammalian central nervous system. This study investigates the cellular and molecular mechanisms underlying mercury-induced neurotoxicity in mammalian brain cells. Studies Using in vitro cultures of primary cortical neurons and astrocytes, as well as in vivo rodent models, have examined the impact of both organic (methylmercury) and inorganic mercury exposure on neuronal viability, oxidative stress, mitochondrial function, and synaptic integrity. Results demonstrate that mercury exposure leads to significant dose- and time-dependent reductions in neuronal survival, primarily mediated by increased production of reactive oxygen species (ROS) and disruption of antioxidant defense systems. Mitochondrial dysfunction was evident through decreased membrane potential and impaired ATP synthesis, contributing to apoptotic and necrotic cell death pathways. Additionally, mercury interfered with calcium homeostasis and glutamate signaling, promoting excitotoxicity and synaptic degeneration. At the molecular level, altered expression of genes associated with inflammation, apoptosis, and neuroprotection was observed, alongside activation of microglial cells, indicating a strong neuroinflammatory response. Histopathological analysis further confirmed structural damage in key brain regions such as the hippocampus and cortex. Overall, the findings highlight the multifaceted neurotoxic effects of mercury on mammalian brain cells and underscore the importance of mitigating environmental and occupational exposure. This study serve to contributes to a deeper understanding of mercury-induced neurodegeneration which may address future therapeutic strategies for neuroprotection.