Orexin A promotes glutamate uptake and inhibits delayed neuronal death in hippocampus CA1 region of transient global cerebral ischemic rats

Abstract

Objective To investigate the effect and mechanism of orexin-A(OX-A) on the expression and function of glial glutamate transporter-1(GLT-1) and delayed neuronal death (DND) in hippocampus CA1 region of transient global cerebral ischemia(tGCI) in rats. Methods The rats were randomized into sham group, model group, OX-A group and OX-A+LY294002 group. The binding and glutamate uptake of GLT-1 in hippocampal CA1 region were detected by the [3H]-glutamate labeling method. The content of glutamate in hippocampal CA1 region was determined by the glutamate quantitative kit. The pathological changes of neurons in hippocampal CA1 region were observed by Nissol, NeuN and Fluro-Jade C staining. The expressions of GLT-1, p-PI3K and p-Akt in hippocampal CA1 region were detected by Western blot. Results OX-A promoted the binding and glutamate uptake of GLT-1, increased glutamate content, GLT-1 expression and PI3K/AKT signaling activity, and inhibited DND in the hippocampal CA1 region of tGCI rats (P＜0.05); However, LY294002 attenuated the above therapeutic effects of OX-A(P＜0.05). Conclusions OX-A can increase the expression and function of GLT-1 and reduce DND in the hippocampal CA1 region of tGCI rats by enhancing the activity of I3K/AKT signal.

Keywords

• orexin-a|ischemic brain injury(ibi)|glt-1|glutamate|delayed neuronal death(dnd)