Khan D, Khan M, Runesson Johan, Zaben M, Gray W P
Institute of Psychological Medicine and Clinical Neurosciences, Neurosciences and Mental Health Research Institute NMHRI, Room 3.33, Hadyn Ellis Building, Cardiff CF24 4HQ, United Kingdom.
Institute of Psychological Medicine and Clinical Neurosciences, Neurosciences and Mental Health Research Institute NMHRI, Room 3.33, Hadyn Ellis Building, Cardiff CF24 4HQ, United Kingdom.
Neuropeptides. 2017 Jun;63:14-17. doi: 10.1016/j.npep.2017.04.002. Epub 2017 Apr 5.
Galanin, a neuropeptide co-released from noradrenergic and serotonergic projection neurons to the dentate gyrus, has recently emerged as an important mediator for signaling neuronal activity to the subgranular neurogenic stem cell niche supporting adult hippocampal neurogenesis. Galanin and its receptors appear to play key roles in depression-like behavior, and effects on hippocampal neurogenesis are relevant to pharmacological strategies for treating depression, which in part appear to rely on restoring altered neurogenesis. We previously demonstrated that the GalR2/3 receptor agonist Gal 2-11 is proliferative and proneurogenic for postnatal hippocampal progenitor cells; however, the specific receptor mediation remained to be identified. With the recent availability of M1145 (a specific GalR2 agonist), and SNAP 37889 (GalR3 specific antagonist), we extend our previous studies and show that while M1145 has no proliferative effect, the co-treatment of postnatal rat hippocampal progenitors with Gal 2-11 and SNAP 37889 completely abolished the Gal 2-11 proliferative effects. Taken together, these results clearly demonstrate that GalR3 and not GalR2 is the specific receptor subtype that mediates the proliferative effects of galanin on hippocampal progenitor cells. These results implicate GALR3 in the mediation of galanin neurogenic effects and, potentially, its neurogenic anti-depressant effects.
甘丙肽是一种与去甲肾上腺素能和5-羟色胺能投射神经元共同释放至齿状回的神经肽，最近已成为向支持成年海马神经发生的颗粒下神经源性干细胞龛传递神经元活动信号的重要介质。甘丙肽及其受体似乎在抑郁样行为中起关键作用，对海马神经发生的影响与治疗抑郁症的药理学策略相关，而这些策略部分似乎依赖于恢复改变的神经发生。我们之前证明，甘丙肽受体2/3激动剂Gal 2-11对出生后海马祖细胞具有增殖和促神经发生作用；然而，具体的受体介导作用仍有待确定。随着最近M1145（一种特异性甘丙肽受体2激动剂）和SNAP 37889（甘丙肽受体3特异性拮抗剂）的可得，我们扩展了之前的研究，结果显示，虽然M1145没有增殖作用，但将出生后大鼠海马祖细胞与Gal 2-11和SNAP 37889共同处理可完全消除Gal 2-11的增殖作用。综上所述，这些结果清楚地表明，介导甘丙肽对海马祖细胞增殖作用的特异性受体亚型是甘丙肽受体3而非甘丙肽受体2。这些结果表明甘丙肽受体3参与介导甘丙肽的神经发生作用，并可能参与其神经发生抗抑郁作用。
