title: Role of Neurexin-1β and Neuroligin-1 in Cognitive Dysfunction After Subarachnoid Hemorrhage in Rats.
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.
authors.affiliation: From the Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, China (H.S., Z.C., Y.W., A.G., H.L., Y.C., L.Z., X.X., Z.W., G.C.); and Department of Neurosurgery, Anhui Provincial Hospital Affiliated to Anhui Medical University, Anhui Province Key Laboratory of Brain Function and Brain Disease, Hefei, Anhui, China (Y.W.).
authors.forename: Haitao
authors.initials: H
authors.lastname: Shen
authors.affiliation: From the Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, China (H.S., Z.C., Y.W., A.G., H.L., Y.C., L.Z., X.X., Z.W., G.C.); and Department of Neurosurgery, Anhui Provincial Hospital Affiliated to Anhui Medical University, Anhui Province Key Laboratory of Brain Function and Brain Disease, Hefei, Anhui, China (Y.W.).
authors.forename: Zhouqing
authors.initials: Z
authors.lastname: Chen
authors.affiliation: From the Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, China (H.S., Z.C., Y.W., A.G., H.L., Y.C., L.Z., X.X., Z.W., G.C.); and Department of Neurosurgery, Anhui Provincial Hospital Affiliated to Anhui Medical University, Anhui Province Key Laboratory of Brain Function and Brain Disease, Hefei, Anhui, China (Y.W.).
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: From the Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, China (H.S., Z.C., Y.W., A.G., H.L., Y.C., L.Z., X.X., Z.W., G.C.); and Department of Neurosurgery, Anhui Provincial Hospital Affiliated to Anhui Medical University, Anhui Province Key Laboratory of Brain Function and Brain Disease, Hefei, Anhui, China (Y.W.).
authors.forename: Anju
authors.initials: A
authors.lastname: Gao
authors.affiliation: From the Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, China (H.S., Z.C., Y.W., A.G., H.L., Y.C., L.Z., X.X., Z.W., G.C.); and Department of Neurosurgery, Anhui Provincial Hospital Affiliated to Anhui Medical University, Anhui Province Key Laboratory of Brain Function and Brain Disease, Hefei, Anhui, China (Y.W.).
authors.forename: Haiying
authors.initials: H
authors.lastname: Li
authors.affiliation: From the Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, China (H.S., Z.C., Y.W., A.G., H.L., Y.C., L.Z., X.X., Z.W., G.C.); and Department of Neurosurgery, Anhui Provincial Hospital Affiliated to Anhui Medical University, Anhui Province Key Laboratory of Brain Function and Brain Disease, Hefei, Anhui, China (Y.W.).
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Cui
authors.affiliation: From the Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, China (H.S., Z.C., Y.W., A.G., H.L., Y.C., L.Z., X.X., Z.W., G.C.); and Department of Neurosurgery, Anhui Provincial Hospital Affiliated to Anhui Medical University, Anhui Province Key Laboratory of Brain Function and Brain Disease, Hefei, Anhui, China (Y.W.).
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: From the Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, China (H.S., Z.C., Y.W., A.G., H.L., Y.C., L.Z., X.X., Z.W., G.C.); and Department of Neurosurgery, Anhui Provincial Hospital Affiliated to Anhui Medical University, Anhui Province Key Laboratory of Brain Function and Brain Disease, Hefei, Anhui, China (Y.W.).
authors.forename: Xiang
authors.initials: X
authors.lastname: Xu
authors.affiliation: From the Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, China (H.S., Z.C., Y.W., A.G., H.L., Y.C., L.Z., X.X., Z.W., G.C.); and Department of Neurosurgery, Anhui Provincial Hospital Affiliated to Anhui Medical University, Anhui Province Key Laboratory of Brain Function and Brain Disease, Hefei, Anhui, China (Y.W.).
authors.forename: Zhong
authors.initials: Z
authors.lastname: Wang
authors.affiliation: From the Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, China (H.S., Z.C., Y.W., A.G., H.L., Y.C., L.Z., X.X., Z.W., G.C.); and Department of Neurosurgery, Anhui Provincial Hospital Affiliated to Anhui Medical University, Anhui Province Key Laboratory of Brain Function and Brain Disease, Hefei, Anhui, China (Y.W.). nju_neurosurgery@163.com dr_zhongwang@126.com.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D003072:Cognition Disorders / Q000378:metabolism* / Q000503:physiopathology*; D004195:Disease Models, Animal; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000378:metabolism*
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D009419:Nerve Tissue Proteins; C093438:neuroligin 1; C086959:neurexin Ibeta
keywords: neurexin-Ibeta; neuroligin 1; stroke; subarachnoid hemorrhage; synapses