SP600125, a competitive inhibitor of JNK attenuates streptozotocin induced neurocognitive deficit and oxidative stress in rats.
Activated JNK has been reported to be located in nucleus in mild cases of Alzheimer's disease (AD), but is exclusively in cytoplasm in more advanced stages of AD and implicated in its pathogenesis, suggesting that activation and re-distribution of JNK correlate with the progress of AD. The present study was designed to investigate the role of JNK in intracerebroventricular streptozotocin (i.c.v. STZ) induced cognitive impairment and oxidative stress. Streptozotocin has been observed to impair learning and memory, increase oxidative-nitritive stress, induce cholinergic hypofunction and neuronal damage in rat brain. Chronic treatment with SP600125 from day 10 to 28 following i.c.v. STZ injections significantly improved spatial memory, attenuate oxidative-nitritive stress. In addition, significant increase in acetylcholinesterase activity and lactate dehydrogenase (LDH) levels was observed in the present model indicating cholinergic hypofunction and increase in neuronal cell damage. Whereas, SP600125 treatment significantly restored acetylcholinesterase activity and reduced LDH levels indicating restorative capacity of SP600125 with respect to cholinergic functions and preventing the neuronal damage. In line with previous report, the current study also supports the potential of JNK inhibition as a possible therapeutic strategy to ameliorate neurodegenerative disorders associated with oxidative stress and cognitive impairment.
Sharma
Nidhi
N
Neuropharmacology Division, Department of Pharmacology, I.S. F. College of Pharmacy, Moga-142001, Punjab, India.
Deshmukh
Rahul
R
Bedi
K L
KL
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology*; D001362:Avoidance Learning; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D003072:Cognition Disorders / Q000139:chemically induced / Q000517:prevention & control*; D005978:Glutathione / Q000378:metabolism; D007276:Injections, Intraventricular; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D051381:Rats; D013311:Streptozocin / Q000008:administration & dosage / Q000633:toxicity*
D000873:Anthracenes; D047428:Protein Kinase Inhibitors; C432165:pyrazolanthrone; D013311:Streptozocin; D007770:L-Lactate Dehydrogenase; D048670:MAP Kinase Kinase 4; D000110:Acetylcholinesterase; D005978:Glutathione