title: Effects of a new synthetic butyrylcholinesterase inhibitor, HBU-39, on cell proliferation and neuroblast differentiation in the hippocampal dentate gyrus in a scopolamine-induced amnesia animal model.
abstract: In this study, we synthesized [1-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-5-(1,2-dithiolan-3-yl)pentan-1-one, HBU-39], a (α)-lipoic acid derivative, and found this compound strongly inhibited butyrylcholinesterase (BuChE) in an in vitro experiment. We also examined the effects of HBU-39 on cell proliferation and neuroblast differentiation using the specific markers Ki67 and doublecortin (DCX), respectively, in the hippocampal dentate gyrus of a rat model of scopolamine-induced amnesia. For this, scopolamine was subcutaneously administered for 28 days by an ALzet osmotic minipump (44 mg/mL delivered at 2.5 μL/h). HBU-39 (1mg/kg per day) and galantamine (an acetylcholinesterase inhibitor used as a control; 5mg/kg per day) were intraperitoneally administered for 28 days. The administration of scopolamine significantly decreased the mean number of Ki67- and DCX-immunoreactive cells in the dentate gyrus. However, treatment with both HBU-39 and galantamine significantly ameliorated the reductions in cell proliferation and neuroblast differentiation. In particular, the mean number of Ki67- and DCX-immunoreactive cells was prominently abundant in the HBU-treated group compared to that in the galantamine-treated group. These results suggest that the BuChE inhibitor, HBU-39, can ameliorate the scopolamine-induced reductions of cell proliferation and neuroblast differentiation, and HBU-39 may be applicable to amnesia patients to promote memory functions.
authors.affiliation: Department of Anatomy and Cell Biology, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul 151-742, South Korea.
authors.forename: Dae Young
authors.initials: DY
authors.lastname: Yoo
authors.forename: Yeun Ji
authors.initials: YJ
authors.lastname: Woo
authors.forename: Woosuk
authors.initials: W
authors.lastname: Kim
authors.forename: Sung Min
authors.initials: SM
authors.lastname: Nam
authors.forename: Bo Hyun
authors.initials: BH
authors.lastname: Lee
authors.forename: Go Heum
authors.initials: GH
authors.lastname: Yeun
authors.forename: Yeo Sung
authors.initials: YS
authors.lastname: Yoon
authors.forename: Moo-Ho
authors.initials: MH
authors.lastname: Won
authors.forename: Jeong Ho
authors.initials: JH
authors.lastname: Park
authors.forename: In Koo
authors.initials: IK
authors.lastname: Hwang
mesh_terms: D000647:Amnesia / Q000139:chemically induced / Q000473:pathology* / Q000523:psychology; D000818:Animals; D002091:Butyrylcholinesterase / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D002802:Cholinesterases / Q000378:metabolism; D018891:Dentate Gyrus / Q000166:cytology* / Q000187:drug effects; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D007150:Immunohistochemistry; D019394:Ki-67 Antigen; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D018727:Muscarinic Antagonists; D009474:Neurons / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012601:Scopolamine; D008063:Thioctic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology*
chemical_list: C569199:1-(4-(benzo(d)(1,3)dioxol-5-ylmethyl)piperazin-1-yl)-5-(1,2-dithiolan-3-yl)pentan-1-one; D002800:Cholinesterase Inhibitors; C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D019394:Ki-67 Antigen; D008869:Microtubule-Associated Proteins; D018727:Muscarinic Antagonists; D009479:Neuropeptides; D010879:Piperazines; D013876:Thiophenes; D008063:Thioctic Acid; D012601:Scopolamine; D002091:Butyrylcholinesterase; D002802:Cholinesterases