Neuroprotective mechanism of Coenzyme Q10 (CoQ10) against PTZ induced kindling and associated cognitive dysfunction: Possible role of microglia inhibition.

Background: Neuroinflammation, oxidative stress and mitochondrial dysfunction play a significant role to explain the pathophysiology of epilepsy. Neuroinflammation through microglia activation has been documented in epileptogenesis. Compounds which inhibit activation of glial cells have been suggested as one of the treatment approaches for the effective treatment of epilepsy. The present study has been designed to investigate the role of coenzyme Q10 and its interaction with minocycline (microglia inhibitor) against pentylenetetrazol (PTZ) induced kindling epilepsy.

Methods: Laca mice received Coenzyme Q10 and minocycline for a period of 29 days. PTZ (40mg/kg ip) injection has been given on alternate days. Various behavioural parameters (kindling score and elevated plus maze), biochemical parameters (lipid peroxidation, superoxide dismutase, reduced glutathione, catalase, nitrite and acetylcholinesterase) and mitochondrial enzyme complex activities of (I, II and IV) were assessed in the discrete areas of the brain.

Results: Administration of a subconvulsive dose of PTZ (40mg/kg) repeatedly increased significantly kindling score, oxidative damage and impaired mitochondrial enzyme complex activities (I, II and IV) and pro-inflammatory marker (TNF-α) as compared to naive animals. Coenzyme Q10 (10, 20 and 40mg/kg) and minocycline (50 and 100mg/kg) for a duration of 29days significantly attenuated kindling score, reversed oxidative damage, TNF-α and restored mitochondrial enzyme complex activities (I, II and IV) as compared to control. Further, combinations of CoQ10 (10, 20mg/kg) with minocycline (50 and 100mg/kg) significantly modulate the protective effect of CoQ10 which was significant as compared to their effect per se in PTZ treated animals.

Conclusion: The present study suggests the involvement of microglia inhibition in the protective effect of CoQ10 in PTZ induced kindling in mice.