title: Donepezil attenuates hippocampal neuronal damage and cognitive deficits after global cerebral ischemia in gerbils.
abstract: Decreased cerebral blood flow causes cognitive impairments and neuronal injury in vascular dementia. In the present study, we reported that donepezil, a cholinesterase inhibitor, improved transient global cerebral ischemia-induced spatial memory impairment in gerbils. Treatment with 5mg/kg of donepezil for 21 consecutive days following a 10-min period of ischemia significantly inhibited delayed neuronal death in the hippocampal CA1 region. In Morris water maze test, memory impairment was significantly improved by donepezil treatment. Western blot analysis showed that donepezil treatment prevented reductions in p-CaMKII and p-CREB protein levels in the hippocampus. These results suggest that donepezil attenuates the memory deficit induced by transient global cerebral ischemia and this neuroprotection may be associated with the phosphorylation of CaMKII and CERB in the hippocampus.
authors.affiliation: Department of Pharmaceutical Toxicology, School of Pharmaceutical Science, China Medical University, Shenyang 110001, China.
authors.forename: Dongyu
authors.initials: D
authors.lastname: Min
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Mao
authors.forename: Kuncan
authors.initials: K
authors.lastname: Wu
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Cao
authors.forename: Feng
authors.initials: F
authors.lastname: Guo
authors.forename: Shu
authors.initials: S
authors.lastname: Zhu
authors.forename: Ni
authors.initials: N
authors.lastname: Xie
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Tianbao
authors.initials: T
authors.lastname: Chen
authors.forename: Chris
authors.initials: C
authors.lastname: Shaw
authors.forename: Jiqun
authors.initials: J
authors.lastname: Cai
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004195:Disease Models, Animal; D000077265:Donepezil; D005849:Gerbillinae; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology* / Q000502:physiology / Q000503:physiopathology; D007189:Indans / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000188:drug therapy* / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D007189:Indans; D018696:Neuroprotective Agents; D010880:Piperidines; D000077265:Donepezil; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2