Manganese overexposure: Unveiling its neurotoxic potential and involvement in pathogenesis of Parkinson's disease.

BACKGROUND: The modern era has brought increased availability of luxurious goods and conveniences, but manufacturing processes of metals and chemicals, including manganese (Mn), pose health risks. Overexposure of Mn is toxic, leading to neurodegenerative diseases like Parkinson's disease (PD) which is characterized by dopaminergic neuronal loss. This study aims to investigates the neurotoxic effects of Mn alone and in combination with rotenone in PD-like pathology.

MATERIAL AND METHODS: Male Wistar rats were treated with manganese chloride (MnCl₂; 15 mg/kg, i.p.) for 28 days. Motor coordination and grip strength were assessed using the strength glass chamber test and string test, respectively. Oxidative stress markers malondialdehyde (MDA) and lactate dehydrogenase (LDH) were measured. Inflammatory marker interleukin-6 (IL-6) and apoptotic marker caspase-3 were quantified using ELISA. Dopamine and glutamate levels were analysed in brain homogenates via reversed-phase high-performance liquid chromatography (RP-HPLC).

RESULTS: MnCl₂ exposure significantly impaired motor coordination and grip strength. Oxidative stress markers (MDA and LDH) and IL-6 levels were markedly elevated in MnCl₂-treated rats compared to controls (p < 0.05). Apoptosis was evident with increased caspase-3 levels (p < 0.05). Neurotransmitter analysis revealed reduced dopamine and elevated glutamate concentrations (p < 0.05). Notably, combining MnCl2 with lower dose of rotenone successfully mimicked PD-like pathology.

CONCLUSION: Chronic Mn exposure induces oxidative stress, inflammation, and neurotransmitter dysregulation, mimicking Parkinsonian neurotoxicity. This study highlights MnCl₂ as a safer alternative to high-dose rotenone for inducing PD-like symptoms for preclinical PD research. The findings underscore the health risks associated with Mn overexposure and its critical role in PD pathogenesis.