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 |
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Authors: | Yoo Dae Young Woo Yeun Ji Kim Woosuk Nam Sung Min Lee Bo Hyun Yeun Go Heum Yoon Yeo Sung Won Moo-Ho Park Jeong Ho Hwang In Koo |
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Affiliation: | a Department of Anatomy and Cell Biology, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul 151-742, South Korea b Division of Applied Chemistry and Biotechnology, Hanbat National University, Daejeon 305-719, South Korea c Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 200-701, South Korea |
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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 (1 mg/kg per day) and galantamine (an acetylcholinesterase inhibitor used as a control; 5 mg/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. |
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Keywords: | HBU-39 Butyrylcholinesterase inhibitor Ki67 Doublecortin Amnesia Dentate gyrus |
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