title: Citalopram Ameliorates Synaptic Plasticity Deficits in Different Cognition-Associated Brain Regions Induced by Social Isolation in Middle-Aged Rats.
abstract: Our previous experiments demonstrated that social isolation (SI) caused AD-like tau hyperphosphorylation and spatial memory deficits in middle-aged rats. However, the underlying mechanisms of SI-induced spatial memory deficits remain elusive. Middle-aged rats (10 months) were group or isolation reared for 8 weeks. Following the initial 4-week period of rearing, citalopram (10 mg/kg i.p.) was administered for 28 days. Then, pathophysiological changes were assessed by performing behavioral, biochemical, and pathological analyses. We found that SI could cause cognitive dysfunction and decrease synaptic protein (synaptophysin or PSD93) expression in different brain regions associated with cognition, such as the prefrontal cortex, dorsal hippocampus, ventral hippocampus, amygdala, and caudal putamen, but not in the entorhinal cortex or posterior cingulate. Citalopram could significantly improve learning and memory and partially restore synaptophysin or PSD93 expression in the prefrontal cortex, hippocampus, and amygdala in SI rats. Moreover, SI decreased the number of dendritic spines in the prefrontal cortex, dorsal hippocampus, and ventral hippocampus, which could be reversed by citalopram. Furthermore, SI reduced the levels of BDNF, serine-473-phosphorylated Akt (active form), and serine-9-phosphorylated GSK-3β (inactive form) with no significant changes in the levels of total GSK-3β and Akt in the dorsal hippocampus, but not in the posterior cingulate. Our results suggest that decreased synaptic plasticity in cognition-associated regions might contribute to SI-induced cognitive deficits, and citalopram could ameliorate these deficits by promoting synaptic plasticity mainly in the prefrontal cortex, dorsal hippocampus, and ventral hippocampus. The BDNF/Akt/GSK-3β pathway plays an important role in regulating synaptic plasticity in SI rats.
authors.affiliation: Department of Neuropsychiatry, Affiliated Zhong Da Hospital, School of Medicine, Southeast University, Nanjing, China.
authors.forename: Wei-Gang
authors.initials: WG
authors.lastname: Gong
authors.affiliation: Department of Neuropsychiatry, Affiliated Zhong Da Hospital, School of Medicine, Southeast University, Nanjing, China.
authors.forename: Yan-Juan
authors.initials: YJ
authors.lastname: Wang
authors.affiliation: Department of Neuropsychiatry, Affiliated Zhong Da Hospital, School of Medicine, Southeast University, Nanjing, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Neuropsychiatry, Affiliated Zhong Da Hospital, School of Medicine, Southeast University, Nanjing, China.
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Li
authors.affiliation: Department of Neuropsychiatry, Affiliated Zhong Da Hospital, School of Medicine, Southeast University, Nanjing, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Bai
authors.affiliation: Department of Neuropsychiatry, Affiliated Zhong Da Hospital, School of Medicine, Southeast University, Nanjing, China. renqingguo1976@163.com.
authors.forename: Qing-Guo
authors.initials: QG
authors.lastname: Ren
authors.affiliation: Department of Neuropsychiatry, Affiliated Zhong Da Hospital, School of Medicine, Southeast University, Nanjing, China.
authors.forename: Zhi-Jun
authors.initials: ZJ
authors.lastname: Zhang
mesh_terms: D000367:Age Factors; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D015283:Citalopram / Q000494:pharmacology / Q000627:therapeutic use*; D003071:Cognition / Q000187:drug effects / Q000502:physiology*; D003072:Cognition Disorders / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D012934:Social Isolation / Q000523:psychology; D065852:Spatial Memory / Q000187:drug effects / Q000502:physiology
chemical_list: D015283:Citalopram; D017367:Selective Serotonin Reuptake Inhibitors
keywords: Alzheimer’s disease; Citalopram; Social isolation; Spatial memory; Synaptic plasticity