Chand Basha Davuljigari
Sri Venkateswara University, India
Title: Decreased aconitase activity potentiates manganese-induced perturbations in mitochondrial apoptotic pathway and dopaminergic system in rats: alleviating effects of nutrient metal mixture
Biography
Biography: Chand Basha Davuljigari
Abstract
The goal of the study was to determine the role of aconitase in dysfunction of the dopaminergic system in Mn-exposed rats. Further, this study aimed to investigate the protective effects of nutrient metal mixture (Calcium, Zinc and Iron) against Mn-induced neurotoxicity. Male pups were exposed to Mn (6mg/Kg body weight) through intraperitoneal injection and the nutrient metal mixture as 0.02% by a single gavage together with Mn separately given from PND 15 to PND 28. The results showed that Mn exposure significantly decreased the synaptosomal dopamine levels and mitochondrial aconitase and monoamine oxidase enzyme activities in the cortex and cerebellum of PND 29, PND 60 and 3 months age groups of rats. Mn treatment significantly down-regulated the expression levels of aconitase, caspase-3, and caspase-9 in the cortex and cerebellum whereas the expression level of tyrosine hydroxylase was up-regulated at PND 29 and downregulated in PND 60 and 3 months age groups of rats. In silico molecular docking results reveal that Mn showed stable binding capacity with aconitase compared to iron binding capacity. Furthermore, histopathological observations showed that marked neuronal degeneration and congestion of blood capillaries in the cerebellum whereas cortex exhibited focal area of vacuolation with marked hemorrhagic lesion and edema following exposure to Mn. However, supplementation of nutrient metal mixture attenuated the Mn-induced impairments in apoptotic markers and mitochondrial enzymes with subsequent restoration of dopamine levels. In conclusion, our findings indicate that decreased activity of aconitase may disrupt mitochondrial apoptotic pathway which can lead to exacerbation of oxidative stress and contribute to neurotoxicity. Further the data suggest that nutrient metal mixture provides protection against Mn-induced neurotoxicity.