MITOCHONDRIAL DYSFUNCTION, OXIDATIVE STRESS & EPILEPSY: A MYSTIFYING TRYST

Author(s): Chaveen Bharti, Nancy Gautam, Dolly Chauhan, Lakshita Dogra, Neha Thakur and Vivek Sharma*

Abstract: Mitochondrial dysfunction and oxidative stress are two interdependent and interconsequent underplaying phenomenon’s which play a critical role in majority of disorders, irrespective of their biochemical pathways and clinical pathologies. Oxidative stress induced mitochondrial dysfunction (and vice versa) has been implicated in pathogenesis of epilepsy too. Epilepsy, a neurological disorder is characterized by the repeated occurrence of seizures due to persistent abnormality in brain circuitry/wiring, an imbalance in inhibitory and excitatory neurotransmitters or some combination of these factors. Primary epilepsy (50%) is idiopathic (unknown cause) and secondary epilepsy (50%), referred as acquired epilepsy, may result from a variety of conditions including trauma, anoxia, hypoxia, metabolic imbalances, tumors, encephalitis, viral infections, drug withdrawal and neurotoxicity. Mitochondrial dysfunction induced oxidative stress increases the cytosolic content of calcium in the cytoplasm through a combination of effects on calcium pumps and membrane integrity. Oxidative stress also affect plasma membrane Ca2+-ATPase, sarco/endoplasmic reticulum ATPase, the IP3 receptor, ryanodine receptors, store-operated calcium entry through Orai channels and voltage-gated calcium channels. In this review, the evidences suggest the role of oxidative stress and mitochondrial dysfunction as consequences of injuries to incite chronic epilepsy and resultant neuropathological changes and present work strongly advocates mitochondrial dysfunction and oxidative stress as the viable and potential therapeutic target in treatment of epileptogenic syndrome.

PAGES: 1153-1160  |  155 VIEWS  340 DOWNLOADS