title: Amelioration of intracerebroventricular streptozotocin induced cognitive dysfunction and oxidative stress by vinpocetine -- a PDE1 inhibitor.
abstract: Enhancing cyclic nucleotides signaling by inhibition of phosphodiesterases (PDEs) is known to be beneficial in disorders associated with cognitive decline. The present study was designed to investigate the effect of vinpocetine (PDE1 inhibitor) on intracerebroventricular (i.c.v.) streptozotocin induced experimental sporadic dementia of Alzheimer's type. Infusion of streptozotocin impaired learning and memory, increased oxidative-nitritive stress and induced cholinergic hypofunction in rats. Chronic treatment with vinpocetine (5, 10 and 20 mg/kg i.p.) for 21 days following first i.c.v. streptozotocin infusion significantly improved learning and memory in Morris water maze and passive avoidance paradigms. Further, vinpocetine significantly reduced the oxidative-nitritive stress, as evidenced by decrease in malondialdehyde (MDA) and nitrite levels, and restored the reduced glutathione (GSH) levels. Significant increase in acetylcholinesterase activity and lactate dehydrogenase levels was observed in the present model indicating cholinergic hypofunction and increase in neuronal cell damage. Chronic treatment with vinpocetine also reduced significantly the increase in acetylcholinesterase activity and lactate dehydrogenase levels indicating restorative capacity of vinpocetine with respect to cholinergic functions and preventing the neuronal damage. The observed beneficial effects of vinpocetine on spatial memory may be due to its ability to favorably modulate cholinergic functions, prevent neuronal cell damage and possibly through its antioxidant mechanism also.
authors.affiliation: Division of Neuropharmacology, Department of Pharmacology, ISF College of Pharmacy, Punjab, India. login2rd@gmail.com
authors.forename: Rahul
authors.initials: R
authors.lastname: Deshmukh
authors.forename: Vivek
authors.initials: V
authors.lastname: Sharma
authors.forename: Sidharth
authors.initials: S
authors.lastname: Mehan
authors.forename: Nidhi
authors.initials: N
authors.lastname: Sharma
authors.forename: K L
authors.initials: KL
authors.lastname: Bedi
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002552:Cerebral Ventricles; D003072:Cognition Disorders / Q000139:chemically induced* / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D005978:Glutathione / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D009573:Nitrites / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin / Q000008:administration & dosage / Q000494:pharmacology*; D014748:Vinca Alkaloids / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D009573:Nitrites; D010726:Phosphodiesterase Inhibitors; D014748:Vinca Alkaloids; D008315:Malondialdehyde; C013983:vinpocetine; D013311:Streptozocin; D007770:L-Lactate Dehydrogenase; D000110:Acetylcholinesterase; D010727:Phosphoric Diester Hydrolases; D005978:Glutathione