Shaikh_2026_Toxicol.Mech.Methods__1

Mercury (Hg) remains a prominent global contaminant despite regulatory interventions such as the Minamata Convention. Inorganic mercury (Hg(2+)), particularly mercuric chloride (HgCl(2)), persists in aquatic ecosystems and poses significant risks to both environmental and human health. While its neurotoxicity is well recognized, the systemic interplay between brain and liver responses under sub-lethal exposure remains poorly understood. Here, we exposed zebrafish (Danio rerio) to an environmentally relevant concentration of HgCl(2) (0.04 ppm) for 15 days to examine behavioural, neurochemical, molecular, and hepatic alterations. Mercury exposure induced pronounced anxiety-like behavior and delayed social recognition, accompanied by decreased locomotor activity. These behavioural deficits are supported with depletion of dopamine, serotonin, and acetylcholinesterase activity, implicating disrupted monoaminergic and cholinergic signaling. Molecular profiling revealed downregulation of aldh1l1 and ugt8, indicating glial dysfunction, and upregulation of il6, consistent with neuroinflammation. In the liver, mercury triggered a shift toward apoptosis (bax/bcl2 ratio increase), inflammation (il6 elevation), and loss of junctional integrity (cldn7a downregulation). Biochemically, exposure to HgCl(2) elevated serum SGPT levels, enhanced lipid peroxidation, and caused dyslipidaemia characterized by reduced HDL, triglyceride, and cholesterol levels. Immunohistochemistry confirmed strong hepatic Hsp90 overexpression, marking oxidative and proteotoxic stress, while histological analysis revealed steatosis, parenchymal disorganization, and nuclear pyknosis. Together, these findings establish that even low-level inorganic mercury exposure perturbs both central and peripheral systems through convergent oxidative and inflammatory mechanisms. Our study highlights mercury as a systemic toxicant disrupting the liver-brain axis and underscores the importance of integrating multi-organ endpoints in environmental risk assessment of heavy metals.