title: ICV STZ induced impairment in memory and neuronal mitochondrial function: A protective role of nicotinic receptor.
abstract: The present study was planned to evaluate the cholinergic influence on mitochondrial activity and neurodegeneration associated with impaired memory in intracerebroventricular (ICV) streptozotocin (STZ) treated rats. STZ (3mg/kg), administered ICV twice with an interval of 48h between the two doses, showed significant impairment in spatial memory tested by water maze test 14 days after first dose without altering blood glucose level and locomotor activity. Animals were sacrificed on 21st day of ICV administration. STZ significantly increased malondialdehyde (MDA), reactive oxygen species (ROS), Ca(2+) ion influx, caspase-3 activity and decreased glutathione (GSH) level. Acetylcholinesterase inhibitors tacrine and donepezil (5mg/kg, PO) pretreatment significantly prevented STZ induced memory deficit, oxidative stress, Ca(2+) influx and caspase-3 activity. Carbachol, a muscarinic cholinergic agonist (0.01mg/kg, SC) did not show any significant effect on ROS generation, Ca(2+) ion influx and caspase-3 activity. While nicotinic cholinergic agonist, nicotine, significantly attenuated ICV STZ induced mitochondrial dysfunction and caspase-3 activity. The results indicate that instead of muscarinic receptors nicotinic receptors may be involved in neuroprotection by maintaining mitochondrial functions.
authors.affiliation: Division of Pharmacology, Central Drug Research Institute (CSIR), Lucknow 226001, India.
authors.forename: Gunjan
authors.initials: G
authors.lastname: Saxena
authors.forename: Ishan K
authors.initials: IK
authors.lastname: Patro
authors.forename: Chandishwar
authors.initials: C
authors.lastname: Nath
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000473:pathology*; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage; D004195:Disease Models, Animal; D000077265:Donepezil; D005978:Glutathione / Q000378:metabolism; D007189:Indans / Q000008:administration & dosage; D007276:Injections, Intraventricular / Q000379:methods; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D009538:Nicotine / Q000008:administration & dosage; D010880:Piperidines / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013311:Streptozocin / Q000633:toxicity*; D013619:Tacrine / Q000008:administration & dosage
chemical_list: D001786:Blood Glucose; D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D017382:Reactive Oxygen Species; D011978:Receptors, Nicotinic; D013619:Tacrine; D008315:Malondialdehyde; D013311:Streptozocin; D009538:Nicotine; D000077265:Donepezil; D053148:Caspase 3; D005978:Glutathione; D002118:Calcium