title: Chronic Cerebral Ischemia Induces Downregulation of A1 Adenosine Receptors During White Matter Damage in Adult Mice.
abstract: The role of A1 adenosine receptors (A1ARs) in the white matter under chronic cerebral ischemic conditions remains unclear. Here, we used right unilateral common carotid artery occlusion (rUCCAO) to construct a chronic cerebral ischemic mouse model. A1AR expression and proteolipid protein (PLP, a marker of white matter myelination) in the corpus callosum were observed by immunoreaction and immunohistochemistry, respectively. Pro-inflammatory interleukin-1β (IL-1β) and anti-inflammatory interleukin-10 (IL-10) levels were determined by ELISA. The Morris water maze test was employed to detect cognitive impairment. A1AR expression significantly decreased in the rUCCAO group as compared with the sham control group on weeks 2, 4, and 6, respectively. IL-10 levels in the rUCCAO group significantly declined on week 6, while there was no significant change in IL-1β expression. PLP expression significantly decreased in the rUCCAO group on weeks 2, 4, and 6. Moreover, latency time for the Morris water maze test significantly increased in the rUCCAO group on weeks 4 and 6, while the number of platform location crossing significantly decreased in the rUCCAO group on weeks 2, 4, and 6. In conclusion, this study provides the first evidence that chronic cerebral ischemia appears to induce A1AR downregulation and inhibition of IL-10 production, which may play key roles in the neuropathological mechanisms of ischemic white matter lesions. These data will facilitate future studies in formulating effective therapeutic strategies for ischemic white matter lesions.
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.|Department of Histology and Embryology, School of Basic Medicine of Jiamusi University, Jiamusi, 154002, Heilongjiang, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Cheng
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Ren
authors.affiliation: Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.|Department of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Shunjie
authors.initials: S
authors.lastname: Bai
authors.affiliation: Department of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.|Department of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Junxi
authors.initials: J
authors.lastname: Pan
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Chen
authors.affiliation: Institute of Neuroscience, Jiamusi University, Jiamusi, 154002, Heilongjiang, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Jiamusi University, Jiamusi, 154002, Heilongjiang, China.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Qi
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Weihua
authors.initials: W
authors.lastname: Shao
authors.affiliation: Department of Neurology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China.
authors.forename: Weiju
authors.initials: W
authors.lastname: Tang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors.forename: Meiling
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China. xiepeng58@21cn.com.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China. xiepeng58@21cn.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Xie
authors.affiliation: Department of Neurology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China. huang_wen@163.com.
authors.forename: Wen
authors.initials: W
authors.lastname: Huang
mesh_terms: D000367:Age Factors; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D002908:Chronic Disease; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D066127:White Matter / Q000378:metabolism* / Q000473:pathology
chemical_list: D043682:Receptor, Adenosine A1
keywords: A1 adenosine receptor; A1AR; Chronic cerebral ischemia; Cognitive impairment; Corpus callosum; Inflammation; Inflammatory; White matter