Histamine up-regulates astrocytic glutamate transporter 1 and protects neurons against ischemic injury
Histamine up-regulates astrocytic glutamate transporter 1 and protects neurons against ischemic injury
复制标题
组胺上调星形胶质细胞谷氨酸转运蛋白 1 并保护神经元免受缺血性损伤
DOI：
10.1016/j.neuropharm.2013.06.012
复制
发表时间：
2014-02-01
影响因子：
4.7
通讯作者：
Chen, Zhong
中科院分区：
文献类型：
--
作者：
Fang, Qi;Hu, Wei-Wei;Chen, Zhong
Astrocytic glutamate transporter 1 (GLT-1) is responsible for the majority of extracellular glutamate clearance and is essential for preventing excitotoxicity in the brain. Up-regulation of GLT-1 shows benefit effect on ischemia-induced neuronal damage. In present study, we examined the effect of histamine, a neurotransmitter or neuromodulator, on GLT-1 expression and function. In acute hippocampal slices, histamine selectively increased GLT-1 expression independent of neuronal activities. Similar up-regulation of GLT-1 was also observed after histamine treatment in pure cultured astrocytes, which was abolished by H1 receptor antagonist or PKC inhibitor. Cell surface biotinylation and whole-cell patch recordings of glutamate transporter current confirmed the up-regulation of functional GLT-1 following histamine exposure. Histamine treatment decreased the extracellular glutamate content and alleviated neuronal cell death induced by exogenous glutamate challenge. Moreover, we found a significant neuroprotective effect of histamine in brain slices after oxygen-glucose deprivation (OGD). In addition, histidine, the precursor of histamine, also showed neuroprotection against ischemic injury, which was accompanied by reversion of declined expression of GLT-1 in adult rats subjected to middle cerebral artery occlusion (MCAO). These neuroprotective effects of histamine/histidine were blocked by GLT-1 specific inhibitor dihydrokainate or H1 receptor antagonist. In summary, our results suggest that histamine up-regulates GLT-1 expression and function via astrocytic H1 receptors, thus resulting in neuroprotection against excitotoxicity and ischemic injury. (C) 2013 Elsevier Ltd. All rights reserved.
