Mercury chloride exposure induces inflammatory and functional disruptions in neurohepatic physiology

Mercury (Hg) remains a prominent global contaminant despite regulatory interventions such as the Minamata Convention. Inorganic mercury (Hg²⁺), particularly mercuric chloride (HgCl₂), 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 (<i>Danio rerio</i>) to an environmentally relevant concentration of HgCl₂ (0.04 ppm) for 15 days to examine behavioral, neurochemical, molecular, and hepatic alterations. Mercury exposure induced pronounced anxiety-like behavior and delayed social recognition, accompanied by decreased locomotor activity. These behavioral deficits are supported with depletion of dopamine, serotonin, and acetylcholinesterase activity, implicating disrupted monoaminergic and cholinergic signaling. Molecular profiling revealed downregulation of <i>aldh1l1</i> and <i>ugt8</i>, indicating glial dysfunction, and upregulation of <i>il6</i>, consistent with neuroinflammation. In the liver, mercury triggered a shift toward apoptosis (<i>bax</i>/<i>bcl2</i> ratio increase), inflammation (<i>il6</i> elevation), and loss of junctional integrity (<i>cldn7a</i> downregulation). Biochemically, exposure to HgCl₂ 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.