Evaluation of Therapeutic Effects of Mecobalamin against Arsenic induced Neurotoxicity in Rats

Abstract

Arsenic contaminated water affected large population of people worldwide and is associated with innumerable disorders of nervous system. Arsenic-induced neurotoxicity leads to disturbance in memory and learning and synaptic plasticity. Cobalamin (Cbl), a water-soluble vitamin, possess positive effect on synaptic plasticity mediated memory and learning in many reported studies. It also possess anti-inflammatory properties while its deficiency is linked with neuronal apoptosis. The study was conducted for examining the cobalamin homologue mecobalamin (MeCbl) effects on the several significant genes expression involved in synaptic plasticity along with antioxidant enzymes activity i.e glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) along with neuronal apoptosis. Sodium arsenate (80 mg/kg) an inducer of neurotoxicity administered along with MeCbl treatment for the period of two months at two selected doses (5 mg and 10 mg per kg of diet) in rats. Results indicated that arsenic treatment induced more significant (p ˂ 0.001) downregulation in the expression of Synaptophysin (Syn), Post Synaptic Density Protein 95 (PSD-95), SH3 And Multiple Ankyrin Repeat Domains 1 (Shank 1), SH3 And Multiple Ankyrin Repeat Domains 2 (Shank 2), Neurexin 2 (Nrxn 2), Neuroligin 1 (Nlgn 1), Kalirin and Calcium/calmodulin-dependent protein kinase IV (CAMK-IV) and less significant (p ˂0.01) downregulation in the expression of Nrxn 1 and Shank 1. The expression of Neuregulin 2 (Nlgn 2) and Synaptosomal associated protein (SNAP-25) was slightly reduced (p ˂ 0.05) while all the study groups showed similar expression of Homer. Arsenic treatment induced oxidative stress leading to substantial decrease (p ˂ 0.001) in antioxidant activity Histopathological examination revealed a significant decrease in cell density in DG (p ˂ 0.001) and CA3, CA1 (p ˂ 0.01) regions of ABSTRACT ix hippocampus after arsenic treatment. Simultaneous treatment with MeCbl (10 mg) resulted in positive shift in the expression of SYN, Shank 1, Shank 2, Nrxn 2, PSD-95, Kalirin and CAMK-IV while the expression of Nlgn 2, SNAP-25 and Nlgn 2 was lower than arsenic treated group. There was increased activity of antioxidant enzymes (SOD, GPx and CAT) in rats with MeCbl treatment relative to arsenic treated rats along with less significant CAT activity in MeCbl (5 mg) treated rats. DG and CA3 regions of the hippocampus showed increased cell count in both MeCbl treated group rats but only MeCbl (10 mg) treated rats were able to recover the cell density in CA1 region of hippocampus. The findings of present study suggest that MeCbl (10 mg/kg) can be an effective option to reverse the changes in synaptic plasticity, histopathology and antioxidant status induced by arsenic