Pyridoxine Modulates 3-Nitropropionic Acid Induced Behavioral as Well as Biochemical Outcomes in Experimental Huntington’s Disease

Abstract:

Background: Huntington’s disease-HD, a neurodegenerative condition developed due to neuronal damage in the brain. 3-nitropropionic acid; 3-NP, a succinate dehydrogenase inhibitor, develops behavioral, biochemical as well as histological alterations in the striatum, resembling HD condition. Pyridoxine, a water-soluble supplement, is employed as an add-on for the treatment of neural disorders. This investigation was framed to analyze the neuro-defensive characteristics of pyridoxine over the 3-NP induced behavioral, striatal, and mitochondrial deficits. Materials and Methods: 3-NP (10 mg kg-1; i.p.) was administered for 14 days on alternate days. Locomotive operation, grip ability, spatial cognition were assessed. Oxidative stress (lipid peroxides, glutathione-GSH, and superoxide dismutase-SOD), cholinergic function (acetylcholinesterase-AChE), inflammation (myeloperoxidase-MPO) and mitochondrial upset (complex I, II and IV) as well as histopathological changes (Nissl stain) were assessed. Results: 3-NP treated animals showed considerable behavioral changes such as decreased locomotion, grip strength, spatial learning memory. 3-NP treated rats exhibited biochemical changes such as increased oxidative stress (enhanced lipid peroxides, reduced GSH, and SOD), disturbed cholinergic function (increased AChE), increased inflammation (more MPO) and mitochondrial dysfunction (reduced complex I, II and IV activity). Chronic neuronal gap, pyknotic nuclei and injured cells have been found in 3-NP treated rats. Tetrabenazine was used as a positive control. Pyridoxine administration considerably restored behavioral, biochemical and histopathological alterations. Conclusion: In this investigation, pyridoxine offered neurodefensive effects which were established by behavioral and biochemical paradigms, confirming the potent neurodefensive aspect of pyridoxine in 3-NP provoked behavioral and biochemical abnormalities.

Key words: Oxidative damage, Cholinergic function, Nissl staining, Striatum, Mitochondrial enzyme complex, Tetrabenazine.