G protein-coupled receptor 37-like 1 modulates astrocyte glutamate transporters and neuronal NMDA receptors and is neuroprotective in ischemia.
G protein-coupled receptor 37-like 1 modulates astrocyte glutamate transporters and neuronal NMDA receptors and is neuroprotective in ischemia.
复制标题
作者：
Jolly S;Bazargani N;Quiroga AC;Pringle NP;Attwell D;Richardson WD;Li H
我们发现，G蛋白偶联受体GPR 37-like 1（GPR 37 L1）在小鼠中枢神经系统的大多数星形胶质细胞和一些少突胶质细胞前体中表达。这与主要存在于成熟少突胶质细胞中的GPR 37形成对比。野生型和GPR 37 L1-/-小鼠的比较表明，GPR 37 L1的缺失不影响海马中星形胶质细胞或神经元的输入电阻或静息电位。然而，GPR 37 L1介导的信号传导抑制星形胶质细胞谷氨酸转运蛋白，并且令人惊讶的是，鉴于其在神经元中缺乏表达，在缺血中发生的受体长时间激活期间降低了神经元NMDA受体（NMDAR）活性。这种对NMDAR信号传导的影响不是由D-丝氨酸或TNF-α释放的变化介导的，这两种星形胶质细胞衍生的药物已知可调节NMDAR功能。大脑中动脉闭塞后，Gpr 37 l1在病灶周围表达增强。在缺血的体外模型中，与野生型相比，Gpr 37 l1-/-脑中的神经元死亡增加了约40%。因此，GPR 37 L1可能通过调节细胞外谷氨酸浓度和NMDAR激活来保护缺血期间的神经元。
We show that the G protein‐coupled receptor GPR37‐like 1 (GPR37L1) is expressed in most astrocytes and some oligodendrocyte precursors in the mouse central nervous system. This contrasts with GPR37, which is mainly in mature oligodendrocytes. Comparison of wild type and Gpr37l1–/– mice showed that loss of GPR37L1 did not affect the input resistance or resting potential of astrocytes or neurons in the hippocampus. However, GPR37L1‐mediated signalling inhibited astrocyte glutamate transporters and – surprisingly, given its lack of expression in neurons – reduced neuronal NMDA receptor (NMDAR) activity during prolonged activation of the receptors as occurs in ischemia. This effect on NMDAR signalling was not mediated by a change in the release of D‐serine or TNF‐α, two astrocyte‐derived agents known to modulate NMDAR function. After middle cerebral artery occlusion, Gpr37l1 expression was increased around the lesion. Neuronal death was increased by ∼40% in Gpr37l1–/– brain compared to wild type in an in vitro model of ischemia. Thus, GPR37L1 protects neurons during ischemia, presumably by modulating extracellular glutamate concentration and NMDAR activation.
登录
查看更多内容
影响因子：
5.3
作者：
Glazner, GW;Mattson, MP
通讯作者：
Mattson, MP
影响因子：
6.2
作者：
Back, Stephen A.;Rosenberg, Paul A.
通讯作者：
Rosenberg, Paul A.
影响因子：
4.7
作者：
Jara, Javier H.;Singh, Brij B.;Combs, Colin K.
通讯作者：
Combs, Colin K.
影响因子：
1.2
作者：
Jolly, Sarah;Fudge, Alexander;Li, Huiliang
通讯作者：
Li, Huiliang
影响因子：
64.8
作者：
通讯作者：
--