title: Effects of donepezil, an acetylcholinesterase inhibitor, on neurogenesis in a rat model of vascular dementia.
abstract: Vascular dementia (VaD) is the second most common form of dementia caused by cerebrovascular disease. Several recent reports demonstrated that cholinergic deficits are implicated in the pathogenesis of VaD and that cholinergic therapies have shown improvement of cognitive function in patients with VaD. However, the precise mechanisms by which donepezil achieves its effects on VaD are not fully understood. Donepezil hydrochloride is an acetylcholinesterase inhibitor (AChEI) currently used for the symptomatic treatment of Alzheimer's disease (AD). Several lines of evidence have demonstrated that AChEIs such as donepezil promote neurogenesis in the central nervous system. We investigated whether donepezil regulated hippocampal neurogenesis after bilateral common carotid artery occlusion (BCCAO) in rats, a commonly used animal model of VaD. To evaluate the effect of donepezil on neurogenesis, we orally treated rats with donepezil (10mg/kg) once a day for 3weeks, and injected BrdU over the same 3-week period to label newborn cells. The doses of donepezil that we used have been reported to activate cholinergic activity in rats. After 3weeks, a water maze task was performed on these rats to test spatial learning, and a subsequent histopathological evaluation was conducted. Donepezil improved memory impairment and increased the number of BrdU-positive cells in the dentate gyrus (DG) of BCCAO animals. These results indicated that donepezil improves cognitive function and enhances the survival of newborn neurons in the DG in our animal model of VaD, possibly by enhancing the expression of choline acetyltransferase and brain-derived neurotropic factor.
authors.affiliation: Department of Neuroscience, Center for Neuroscience Research, Institute of Biomedical Science and Technology, Konkuk University School of Medicine, Republic of Korea.
authors.forename: Kyoung Ja
authors.initials: KJ
authors.lastname: Kwon
authors.affiliation: Department of Neuroscience, Center for Neuroscience Research, Institute of Biomedical Science and Technology, Konkuk University School of Medicine, Republic of Korea.
authors.forename: Min Kyeong
authors.initials: MK
authors.lastname: Kim
authors.affiliation: Department of Neuroscience, Center for Neuroscience Research, Institute of Biomedical Science and Technology, Konkuk University School of Medicine, Republic of Korea.
authors.forename: Eun Joo
authors.initials: EJ
authors.lastname: Lee
authors.affiliation: Department of Neuroscience, Center for Neuroscience Research, Institute of Biomedical Science and Technology, Konkuk University School of Medicine, Republic of Korea.
authors.forename: Jung Nam
authors.initials: JN
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, Center for Neuroscience Research, Institute of Biomedical Science and Technology, Konkuk University School of Medicine, Republic of Korea.
authors.forename: Bo-Ryoung
authors.initials: BR
authors.lastname: Choi
authors.affiliation: Department of Pharmacology, Center for Neuroscience Research, Institute of Biomedical Science and Technology, Konkuk University School of Medicine, Republic of Korea.
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Neuroscience, Center for Neuroscience Research, Institute of Biomedical Science and Technology, Konkuk University School of Medicine, Republic of Korea.
authors.forename: Kyu Suk
authors.initials: KS
authors.lastname: Cho
authors.affiliation: Department of Biological Sciences, Center for Neuroscience Research, Institute of Biomedical Science and Technology, Konkuk University School of Medicine, Republic of Korea.
authors.forename: Jung-Soo
authors.initials: JS
authors.lastname: Han
authors.affiliation: Department of Neuroscience, Center for Neuroscience Research, Institute of Biomedical Science and Technology, Konkuk University School of Medicine, Republic of Korea; Department of Neurology, Konkuk University Medical Center, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of Korea.
authors.forename: Hahn Young
authors.initials: HY
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, Center for Neuroscience Research, Institute of Biomedical Science and Technology, Konkuk University School of Medicine, Republic of Korea.
authors.forename: Chan Young
authors.initials: CY
authors.lastname: Shin
authors.affiliation: Department of Neuroscience, Center for Neuroscience Research, Institute of Biomedical Science and Technology, Konkuk University School of Medicine, Republic of Korea; Department of Neurology, Konkuk University Medical Center, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of Korea. Electronic address: alzdoc@kuh.ac.kr.
authors.forename: Seol-Heui
authors.initials: SH
authors.lastname: Han
mesh_terms: D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects*; D015140:Dementia, Vascular / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects; D004195:Disease Models, Animal; D000077265:Donepezil; D007189:Indans / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D055495:Neurogenesis / Q000187:drug effects*; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil
keywords: Acetylcholinesterase; Cognitive function; Glia; MAPK; Neurogenesis; Vascular dementia