title: Galantamine promotes adult hippocampal neurogenesis via M₁ muscarinic and α7 nicotinic receptors in mice.
abstract: Galantamine, an inhibitor of acetylcholinesterase, promotes hippocampal neurogenesis, but the exact mechanism for this is not known. 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 5-bromo-2'-deoxyuridine (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 antagonists mecamylamine and methyllycaconitine. Galantamine did not alter the ratio of neuronal nuclei (NeuN)- or glial fibrillary acidic protein (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-wk-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 wk. 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-wk-old immature cells in the granule cell layer.
authors.affiliation: Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences,Osaka University,1-6 Yamada-oka, Suita, Osaka 565-0871,Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kita
authors.affiliation: Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences,Osaka University,1-6 Yamada-oka, Suita, Osaka 565-0871,Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ago
authors.affiliation: Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences,Osaka University,1-6 Yamada-oka, Suita, Osaka 565-0871,Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Higashino
authors.affiliation: Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences,Osaka University,1-6 Yamada-oka, Suita, Osaka 565-0871,Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Asada
authors.affiliation: Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences,Osaka University,1-6 Yamada-oka, Suita, Osaka 565-0871,Japan.
authors.forename: Erika
authors.initials: E
authors.lastname: Takano
authors.affiliation: Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences,Osaka University,1-6 Yamada-oka, Suita, Osaka 565-0871,Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Takuma
authors.affiliation: Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences,Osaka University,1-6 Yamada-oka, Suita, Osaka 565-0871,Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Matsuda
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004268:DNA-Binding Proteins; D004305:Dose-Response Relationship, Drug; D005702:Galantamine / Q000494:pharmacology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D008297:Male; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009687:Nuclear Proteins / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D043643:Receptor, Muscarinic M1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; C513121:IGF2 protein, mouse; D009419:Nerve Tissue Proteins; C492380:NeuN protein, mouse; D018696:Neuroprotective Agents; D009687:Nuclear Proteins; D043643:Receptor, Muscarinic M1; D011994:Recombinant Proteins; D064569:alpha7 Nicotinic Acetylcholine Receptor; D005702:Galantamine; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1