title: Chronic cerebral hypoperfusion induces long-lasting cognitive deficits accompanied by long-term hippocampal silent synapses increase in rats.
abstract: Synaptic dysfunction underlies cognitive deficits induced by chronic cerebral hypoperfusion (CCH). There are silent synapses in neural circuits, but the effect of CCH on silent synapses is unknown. The present study was designed to explore learning and memory deficits and dynamic changes in silent synapses by direct visualization in a rat model of CCH. Adult male Sprague-Dawley rats were subjected to permanent bilateral common carotid artery occlusion (BCCAO) to reproduce CCH. Learning and memory effects were examined at 1, 4, 12, and 24 weeks after BCCAO. In addition, immunofluorescent confocal microscopy was used to detect AMPA and N-methyl-d-aspartate receptors colocalized with synaptophysin, and Golgi-Cox staining was used to observe dendritic spine density. We found that BCCAO rats exhibited recognition memory deficits from 4 weeks; spatial learning and memory, as well as working memory impairment began at 1 week and persistent to 24 weeks after surgery. Following BCCAO, the percentage of silent synapses increased by 29.81-55.08% compared with the controls at different time points (P<0.001). Compared with control groups, dendritic spine density in the CA1 region of BCCAO groups significantly decreased (P<0.001). Thus, the present study suggests that CCH can induce long-lasting cognitive deficits and long-term increase in the number of silent synapses. Furthermore, the decrease in dendritic spine density was correlated with the decrease in the number of functional synapses. The results suggest a potential mechanism by which CCH can induce learning and memory deficits.
authors.affiliation: The Graduate Management Team, The Third Military Medical University, Chongqing 400038, China; Department of Neurology, Chengdu Military General Hospital, Chengdu 610083, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Neurology, Chengdu Military General Hospital, Chengdu 610083, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Fan
authors.affiliation: Department of Neurology, Chengdu Military General Hospital, Chengdu 610083, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Neurology, Chengdu Military General Hospital, Chengdu 610083, China.
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Neurology, Chengdu Military General Hospital, Chengdu 610083, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Duan
authors.affiliation: Department of Neurology, Chengdu Military General Hospital, Chengdu 610083, China.
authors.forename: Guo
authors.initials: G
authors.lastname: Du
authors.affiliation: Department of Neurology, Chengdu Military General Hospital, Chengdu 610083, China. Electronic address: wqs832001@sina.com.
authors.forename: Qingsong
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000818:Animals; D002561:Cerebrovascular Disorders / Q000150:complications / Q000473:pathology / Q000503:physiopathology* / Q000523:psychology; D002908:Chronic Disease; D003072:Cognition Disorders / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D049229:Dendritic Spines / Q000473:pathology / Q000502:physiology; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008570:Memory, Short-Term / Q000502:physiology; D018613:Microscopy, Confocal; D017966:Pyramidal Cells / Q000473:pathology / Q000502:physiology; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D021641:Recognition, Psychology / Q000502:physiology; D065852:Spatial Memory / Q000502:physiology; D013569:Synapses / Q000473:pathology / Q000502:physiology*; D016708:Synaptophysin / Q000378:metabolism
chemical_list: D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D016708:Synaptophysin
keywords: Chronic cerebral hypoperfusion; Hippocampus; Ionotropic glutamate receptor; Silent synapse; Vascular dementia