Shen_2015_Stroke_46_2607

BACKGROUND AND PURPOSE: Neurexin-1beta and neuroligin-1 play an important role in the formation, maintenance, and regulation of synaptic structures. This study is to estimate the potential role of neurexin-1beta and neuroligin-1 in subarachnoid hemorrhage (SAH)-induced cognitive dysfunction.
METHODS: In vivo, 228 Sprague-Dawley rats were used. An experimental SAH model was induced by single blood injection to prechiasmatic cistern. Primary cultured hippocampal neurons were exposed to oxyhemoglobin to mimic SAH in vitro. Specific small interfering RNAs and expression plasmids for neurexin-1beta and neuroligin-1 were exploited both in vivo and in vitro. Western blot, immunofluorescence, immunoprecipitation, neurological scoring, and Morris water maze were performed to evaluate the mechanism of neurexin-1beta and neuroligin-1, as well as neurological outcome.
RESULTS: Both in vivo and in vitro experiments showed SAH-induced decrease in the expressions of neurexin-1beta and neuroligin-1 and the interaction between neurexin-1beta and neuroligin-1 in neurons. In addition, the interaction between neurexin-1beta and neuroligin-1 was reduced by their knockdown and increased by their overexpression. The formation of excitatory synapses was inhibited by oxyhemoglobin treatment, which was significantly ameliorated by overexpression of neurexin-1beta and neuroligin-1 and aggravated by the knockdown of neurexin-1beta and neuroligin-1. More importantly, neurexin-1beta and neuroligin-1 overexpression ameliorated SAH-induced cognitive dysfunction, whereas neurexin-1beta and neuroligin-1 knockdown induced an opposite effect.
CONCLUSIONS: Enhancing the expressions of neurexin-1beta and neuroligin-1 could promote the interaction between them and the formation of excitatory synapses, which is helpful to improve cognitive dysfunction after SAH. Neurexin-1beta and neuroligin-1 might be good targets for improving cognitive function after SAH.