Galantamine promotes adult hippocampal neurogenesis via M1 muscarinic and α7 nicotinic receptors in mice
Galantamine promotes adult hippocampal neurogenesis via M1 muscarinic and α7 nicotinic receptors in mice
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DOI：
10.1017/s1461145714000613
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发表时间：
2014-12-01
影响因子：
4.8
通讯作者：
Matsuda, Toshio
中科院分区：
文献类型：
--
作者：
Kita, Yuki;Ago, Yukio;Matsuda, Toshio
乙酰胆碱酯酶抑制剂加兰他敏促进海马神经发生，但其确切机制尚不清楚。在本研究中，我们研究了急性加兰他敏对小鼠海马神经发生的影响的机制。加兰他敏（3 mg/kg）可增加齿状回颗粒下区5-溴-2 '-脱氧尿苷（BrdU）阳性细胞的数量。这种作用被阻断的毒蕈碱受体拮抗剂东莨菪碱和M-1毒蕈碱受体拮抗剂telenzepine的优先，但不是由烟碱受体拮抗剂美加明和methylycaconitine。加兰他敏并没有改变神经元核（NeuN）或胶质细胞酸性蛋白（GFAP）阳性细胞的比例BrdU标记的细胞在颗粒下区和颗粒细胞层。加兰他敏（1，3 mg/kg）促进小鼠齿状回颗粒细胞层中2周龄新分裂细胞的存活，而它不影响1和4周龄新分裂细胞的存活。加兰他敏诱导的细胞存活率的增加被α 7烟碱受体拮抗剂methylycaconitine阻断，但东莨菪碱不能阻断。双侧注射重组IGF 2到海马齿状回模仿加兰他敏的影响。直接注射IGF 1受体拮抗剂JB 1可阻断加兰他敏的作用。这些发现表明加兰他敏通过激活M-1毒蕈碱和α 7烟碱乙酰胆碱受体促进神经发生。本研究还表明，IGF 2参与加兰他敏对颗粒细胞层中2周龄未成熟细胞存活的影响。
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 M-1 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 alpha 7 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 M-1 muscarinic and alpha 7 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.