Protective role of sertraline against 3-nitropropionic acid-induced cognitive dysfunction and redox ratio in striatum, cortex and hippocampus of rat brain.
Huntington's disease (HD) is an inherited progressive neurodegenerative disorder in human characterized by progressive loss of movement and cognitive disturbances. 3-nitropropionic acid (3-NP; a mitochondrial toxin) produces age-dependent oxidative linked striatal damage, responsible for HD like symptoms. In the present study protective effect of sertraline in 3-NP induced HD like symptoms was evaluated in rats. Systemic administration of 3-NP (10 mg/kg for 14 days) resulted in impairment of memory as assessed in Morris water maze and elevated plus paradigm tasks. Biochemical analysis revealed that systemic 3-NP administration significantly impaired reduced glutathione, total glutathione, oxidized glutathione and glutathione-S-transferase levels, whereas the level of acetylcholinesterase enzyme increased in striatum, cortex and hippocampus regions of rat brain. Sertraline (5 and 10 mg/kg po) treatment once daily for 14 days significantly improved cognitive performance tasks and glutathione levels in 3-NP treated group. However, combination of yohimbine (2 mg/kg) (non selective serotonin receptors antagonist) with the higher dose of sertraline (10 mg/kg) did not influence the protective action of sertraline. Result shows that neuroprotective and antioxidant like effect of sertraline is independent of its conventional action on 5-HT receptor.
Kumar
Puneet
P
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India.
Kumar
Anil
A
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000633:toxicity; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects*; D003072:Cognition Disorders / Q000139:chemically induced / Q000517:prevention & control*; D003342:Corpus Striatum / Q000187:drug effects*; D005978:Glutathione / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009498:Neurotoxins / Q000633:toxicity; D009574:Nitro Compounds / Q000633:toxicity*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D011422:Propionates / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D020280:Sertraline / Q000494:pharmacology*
D000928:Antidepressive Agents; D000959:Antihypertensive Agents; D009498:Neurotoxins; D009574:Nitro Compounds; D011422:Propionates; D000110:Acetylcholinesterase; D005978:Glutathione; D020280:Sertraline; C015392:3-nitropropionic acid