Dynamin-related Protein 1 Inhibition Mitigates Bisphenol A-mediated Alterations in Mitochondrial Dynamics and Neural Stem Cell Proliferation and Differentiation
作者： Swati Agarwal , Anuradha Yadav , Shashi Kant Tiwari , Brashket Seth , Lalit Kumar Singh Chauhan
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摘要: The regulatory dynamics of mitochondria comprises well orchestrated distribution and mitochondrial turnover to maintain the circuitry homeostasis inside cells. Several pieces evidence suggested impaired its association with pathogenesis neurodegenerative disorders. We found that chronic exposure synthetic xenoestrogen bisphenol A (BPA), a component consumer plastic products, autophagy-mediated turnover, leading increased oxidative stress, fragmentation, apoptosis in hippocampal neural stem cells (NSCs). It also inhibited derived NSC proliferation differentiation, as evident by decreased number BrdU- β-III tubulin-positive All these effects were reversed inhibition stress using N-acetyl cysteine. BPA up-regulated levels Drp-1 (dynamin-related protein 1) enhanced translocation, no effect on Fis-1, Mfn-1, Mfn-2, Opa-1 vitro hippocampus. Moreover, transmission electron microscopy studies fission accumulation fragmented elongated hippocampus rat brain. Impaired resulted reactive oxygen species malondialdehyde levels, disruption membrane potential, ATP decline. Pharmacological (Mdivi-1) genetic (Drp-1siRNA) BPA-induced dysfunctions, apoptosis. Interestingly, BPA-mediated inhibitory neuronal differentiations mitigated inhibition. On other hand, blocked NSC. Overall, our implicate potential therapeutic target against neurodegeneration
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