Melatonin attenuates branch chain fatty acid induced apoptosis mediated neurodegeneration

Valproic acid (VPA)-a short branched chain fatty acid (BCFA), is widely recognized as an anticonvulsant and a mood-stabilizing drug, but various adverse effects of VPA have also been investigated. However, the impact of BCFAs aggregation on brain cells, in the pathogenesis of neurodegeneration remains elusive. The objective of this study is to understand the cellular mechanisms underlying VPA-induced neuronal cell death mediated by oxidative stress, and the neuroprotective role of exogenous melatonin treatment on VPA-induced cell death. Neurotoxicity of VPA and protective role exerted by melatonin were assessed in vitro in SH-SY5Y cells and in vivo in the cerebral cortex and cerebellum regions of Wistar rat brain. The results show that melatonin pre-treatment protects the cells from VPA-induced toxicity by exerting an anti-apoptotic and anti-inflammatory effect by regulating apoptotic proteins and pro-inflammatory cytokines. The findings of the present study emphasize novel insights of melatonin as a supplement for the prevention and treatment of neuronal dysfunction induced by VPA.