Histamine up-regulates astrocytic glutamate transporter 1 and protects neurons against ischemic injury.

作者: Qi Fang , Wei-Wei Hu , Xiao-Fen Wang , Yang Yang , Guo-Dong Lou

DOI: 10.1016/J.NEUROPHARM.2013.06.012

关键词: Glutamate aspartate transporterHistamine H1 receptorNeuroprotectionBiochemistryBiologyHistamine H3 receptorHistamine trifluoromethyl toluidideHistaminePharmacologyGlutamate receptorExcitotoxicity

摘要: Astrocytic glutamate transporter 1 (GLT-1) is responsible for the majority of extracellular clearance and essential preventing excitotoxicity in brain. Up-regulation GLT-1 shows benefit effect on ischemia-induced neuronal damage. In present study, we examined histamine, a neurotransmitter or neuromodulator, expression function. acute hippocampal slices, histamine selectively increased independent activities. Similar up-regulation was also observed after treatment pure cultured astrocytes, which abolished by H1 receptor antagonist PKC inhibitor. Cell surface biotinylation whole-cell patch recordings current confirmed functional following exposure. Histamine decreased content alleviated cell death induced exogenous challenge. Moreover, found significant neuroprotective brain slices oxygen-glucose deprivation (OGD). addition, histidine, precursor showed neuroprotection against ischemic injury, accompanied reversion declined adult rats subjected to middle cerebral artery occlusion (MCAO). These effects histamine/histidine were blocked specific inhibitor dihydrokainate antagonist. summary, our results suggest that up-regulates function via astrocytic receptors, thus resulting injury.

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