Activation of the galanin receptor 2 (GalR2) protects the hippocampus from neuronal damage.
Activation of the galanin receptor 2 (GalR2) protects the hippocampus from neuronal damage.
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DOI：
10.1111/j.1471-4159.2006.04239.x
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发表时间：
2007-02
影响因子：
4.7
通讯作者：
Wynick D
中科院分区：
文献类型：
--
作者：
Elliott-Hunt CR;Pope RJ;Vanderplank P;Wynick D
神经肽甘丙肽的表达在神经损伤后的许多脑区和阿尔茨海默病患者的基底前脑中上调。我们先前已经证明甘丙肽调节海马神经元的存活，尽管尚不清楚哪种受体亚型介导这种效应。在这里，我们报告说，在海马培养中发挥的保护作用的甘丙肽被废除的动物携带的功能丧失突变的第二甘丙肽受体亚型（GalR 2-MUT）。外源性甘丙肽刺激野生型（WT）培养物中丝氨酸/苏氨酸激酶Akt和细胞外信号调节激酶（ERK）的磷酸化，分别为435 ± 5%和278 ± 2%。谷氨酸诱导的Akt活化在甘丙肽敲除动物的培养物中被消除，并且与WT对照相比，在GalR 2-MUT动物中显著减弱。相反，在两种功能丧失突变体中观察到类似水平的谷氨酸诱导的ERK激活，但在甘丙肽过表达动物中进一步增加。使用ERK或Akt的特异性抑制剂证实了Akt和ERK信号传导途径活化中的GalR 2依赖性调节有助于甘丙肽的保护作用。这些发现意味着在脑损伤后或在各种疾病状态中观察到的内源性甘丙肽的升高是一种适应性反应，其通过激活GalR 2以及因此Akt和ERK来减少细胞凋亡。
Expression of the neuropeptide galanin is up-regulated in many brain regions following nerve injury and in the basal forebrain of patients with Alzheimer’s disease. We have previously demonstrated that galanin modulates hippocampal neuronal survival, although it was unclear which receptor subtype(s) mediates this effect. Here we report that the protective role played by galanin in hippocampal cultures is abolished in animals carrying a loss-of-function mutation in the second galanin receptor subtype (GalR2-MUT). Exogenous galanin stimulates the phosphorylation of the serine/threonine kinase Akt and extracellular signal-regulated kinase (ERK) in wild-type (WT) cultures by 435 ± 5% and 278 ± 2%, respectively. The glutamate-induced activation of Akt was abolished in cultures from galanin knockout animals, and was markedly attenuated in GalR2-MUT animals, compared with WT controls. In contrast, similar levels of glutamate-induced ERK activation were observed in both loss-of-function mutants, but were further increased in galanin over-expressing animals. Using specific inhibitors of either ERK or Akt confirms that a GalR2-dependent modulation in the activation of the Akt and ERK signalling pathways contributes to the protective effects of galanin. These findings imply that the rise in endogenous galanin observed either after brain injury or in various disease states is an adaptive response that reduces apoptosis by the activation of GalR2, and hence Akt and ERK.
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影响因子：
5.3
作者：
Chang, SH;Poser, S;Xia, ZG
通讯作者：
Xia, ZG
DOI：
10.1016/s0169-328x(97)00070-3
发表时间：
1997-08-01
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Brecht, S;Buschmann, T;Herdegen, T
通讯作者：
Herdegen, T
DOI：
10.1016/s0169-328x(97)00210-6
发表时间：
1997-11-01
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Fathi, Z;Cunningham, AM;Zimanyi, IA
通讯作者：
Zimanyi, IA
DOI：
10.1073/pnas.161293598
发表时间：
2001-08-14
影响因子：
11.1
作者：
Liu, HX;Brumovsky, P;Hökefelt, T
通讯作者：
Hökefelt, T
影响因子：
4.7
作者：
Gary, DS;Milhavet, O;Mattson, MP
通讯作者：
Mattson, MP