Abstract：
OBJECTIVE: Neurexin-1β 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-1β 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-1β 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-1β 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-1β and neuroligin-1 and the interaction between neurexin-1β and neuroligin-1 in neurons. In addition, the interaction between neurexin-1β 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-1β and neuroligin-1 and aggravated by the knockdown of neurexin-1β and neuroligin-1. More importantly, neurexin-1β and neuroligin-1 overexpression ameliorated SAH-induced cognitive dysfunction, whereas neurexin-1β and neuroligin-1 knockdown induced an opposite effect.
CONCLUSIONS: Enhancing the expressions of neurexin-1β 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-1β and neuroligin-1 might be good targets for improving cognitive function after SAH.
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-1β 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-1β 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-1β and neuroligin-1 and the interaction between neurexin-1β and neuroligin-1 in neurons. In addition, the interaction between neurexin-1β 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-1β and neuroligin-1 and aggravated by the knockdown of neurexin-1β and neuroligin-1. More importantly, neurexin-1β and neuroligin-1 overexpression ameliorated SAH-induced cognitive dysfunction, whereas neurexin-1β and neuroligin-1 knockdown induced an opposite effect.
CONCLUSIONS: Enhancing the expressions of neurexin-1β 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-1β and neuroligin-1 might be good targets for improving cognitive function after SAH.
摘要：
目的：Neurexin-1β和Neuroligin-1在其形成中起重要作用，维护,和调节突触结构。本研究旨在评估neurexin-1β和neuroligin-1在蛛网膜下腔出血（SAH）引起的认知功能障碍中的潜在作用。
方法：体内，使用228只Sprague-Dawley大鼠。通过单次血液注射到前腔池来诱导实验性SAH模型。将原代培养的海马神经元暴露于氧合血红蛋白以在体外模拟SAH。在体内和体外都开发了针对nurexin-1β和neuroligin-1的特异性小干扰RNA和表达质粒。蛋白质印迹,免疫荧光，免疫沉淀,神经学评分,和Morris水迷宫进行评估，以评估Neurexin-1β和Neuroligin-1的机制以及神经系统的预后。
结果：体内和体外实验均显示SAH诱导的神经元中neurexin-1β和neuroligin-1的表达减少，以及neurexin-1β和neuroligin-1之间的相互作用。此外,Neurexin-1β和Neuroligin-1之间的相互作用因它们的敲低而减少，并因它们的过表达而增加。通过氧合血红蛋白处理抑制兴奋性突触的形成,nurexin-1β和neuroligin-1的过表达显着改善，而nurexin-1β和neuroligin-1的敲低则加重。更重要的是,神经肽-1β和神经凝集素-1过表达改善SAH诱导的认知功能障碍，而neurexin-1β和neuroligin-1敲低诱导相反的作用。
结论：增强Neurexin-1β和Neuroligin-1的表达可以促进它们之间的相互作用和兴奋性突触的形成。有助于改善SAH后认知功能障碍。Neurexin-1β和Neuroligin-1可能是改善SAH后认知功能的良好靶点。
方法：体内，使用228只Sprague-Dawley大鼠。通过单次血液注射到前腔池来诱导实验性SAH模型。将原代培养的海马神经元暴露于氧合血红蛋白以在体外模拟SAH。在体内和体外都开发了针对nurexin-1β和neuroligin-1的特异性小干扰RNA和表达质粒。蛋白质印迹,免疫荧光，免疫沉淀,神经学评分,和Morris水迷宫进行评估，以评估Neurexin-1β和Neuroligin-1的机制以及神经系统的预后。
结果：体内和体外实验均显示SAH诱导的神经元中neurexin-1β和neuroligin-1的表达减少，以及neurexin-1β和neuroligin-1之间的相互作用。此外,Neurexin-1β和Neuroligin-1之间的相互作用因它们的敲低而减少，并因它们的过表达而增加。通过氧合血红蛋白处理抑制兴奋性突触的形成,nurexin-1β和neuroligin-1的过表达显着改善，而nurexin-1β和neuroligin-1的敲低则加重。更重要的是,神经肽-1β和神经凝集素-1过表达改善SAH诱导的认知功能障碍，而neurexin-1β和neuroligin-1敲低诱导相反的作用。
结论：增强Neurexin-1β和Neuroligin-1的表达可以促进它们之间的相互作用和兴奋性突触的形成。有助于改善SAH后认知功能障碍。Neurexin-1β和Neuroligin-1可能是改善SAH后认知功能的良好靶点。
