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Alzheimer's Disease, Other Dementia, Aging

開催日 2014/9/11
時間 11:00 - 12:00
会場 Poster / Exhibition(Event Hall B)

Stimulation of adult hippocampal neurogenesis by galantamine in mice: roles of M1 muscarinic and α7 nicotinic receptors

  • P1-291
  • 東野 功典 / Kosuke Higashino:1 喜多 祐紀 / Yuki Kita:1 浅田 和希 / Kazuki Asada:1 高野 恵利加 / Erika Takano:1 吾郷 由希夫 / yukio Ago:1 田熊 一敞 / Kazuhiro Takuma:1 松田 敏夫 / Toshio Matsuda:1,2 
  • 1:大阪大院・薬・薬物治療 / Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University 2:大阪大院・連合小児発達 / United Graduate School of Child Development, Osaka University 

Galantamine, an inhibitor of acetylcholinesterase, is used for patients with Alzheimer's disease. It is reported that chronic administration of galantamine promotes neurogenesis in the mice hippocampus. We have recently demonstrated that galantamine increased hippocampal insulin-like growth factor 2 (IGF2) expression via activation of the α7 nicotinic receptor in mice (Psychopharmacology, 2013). However, the exact mechanism of neurogenesis by the galantamine is not clear. In the present study, we examined the mechanisms underlying the effects of acute galantamine on neurogenesis in the mouse hippocampus. Galantamine (3 mg/kg) increased the number of BrdU-positive cells in the subgranular zone of the dentate gyrus. This effect was blocked by the muscarinic receptor antagonist scopolamine and the preferential M1 muscarinic receptor antagonist telenzepine, but not by the nicotinic receptor antagonist mecamylamine. Galantamine did not alter the ratio of NeuN- or GFAP-positive cells to BrdU-labeled cells in the subgranular zone and granule cell layer. Galantamine (1, 3 mg/kg) promoted the survival of 2-week-old newly divided cells in mice in the granule cell layer of the dentate gyrus, whereas it did not affect the survival of newly divided cells at 1 and 4 weeks. Galantamine-induced increases in cell survival were blocked by the α7 nicotinic receptor antagonist methyllycaconitine, but not by scopolamine. Bilateral injection of recombinant IGF2 into the dentate gyrus of the hippocampus mimicked the effects of galantamine. The effects of galantamine were blocked by direct injection of the IGF1 receptor antagonist JB1. These findings suggest that galantamine promotes neurogenesis via activation of the M1 muscarinic and α7 nicotinic acetylcholine receptors. The present study also suggests that IGF2 is involved in the effects of galantamine on the survival of 2-week-old immature cells in the granule cell layer.

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