title: Citalopram attenuates tau hyperphosphorylation and spatial memory deficit induced by social isolation rearing in middle-aged rats.
abstract: Social isolation (SI) is considered as a chronic stress. Here, middle-aged rats (8 months) were group or isolation reared for 6 weeks. Following the initial two-week period of rearing, citalopram (10 mg/kg i.p.) was administered for 28 days. Changes in recognition memory, depression and anxiety-like behavior, and phosphorylated tau were investigated. We found that SI did not lead to obvious depression/anxiety-like behavior in middle-aged rats. Memory deficits and increased tau hyperphosphorylation at Tau-1, Ser396 episodes could be almost reversed by citalopram. The level of Ser9-phosphorylated GSK-3β (inactive form) was significantly decreased in the SI group which also could be almost reversed by citalopram, suggesting that the citalopram could prevent GSK-3β from SI-induced overactivation. The melatonin level was decreased in SI group compared with group housed (GH) group, and citalopram could partly restore the level of melatonin. We also found that citalopram could increase MT1 and MT2 in mRNA level. Our results demonstrate that citalopram increases the level of melatonin which negatively regulates GSK-3β and attenuates tau hyperphosphorylation and spatial memory deficit induced by SI in middle-aged rats. Suggesting that SI might constitute a risk factor for Alzheimer's disease (AD), and citalopram may represent a therapeutic strategy for the treatment of AD.
authors.affiliation: Department of Neuropsychiatry, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, China, rqg1976@tom.com.
authors.forename: Qing-Guo
authors.initials: QG
authors.lastname: Ren
authors.forename: Wei-Gang
authors.initials: WG
authors.lastname: Gong
authors.forename: Yan-Juan
authors.initials: YJ
authors.lastname: Wang
authors.forename: Qi-Da
authors.initials: QD
authors.lastname: Zhou
authors.forename: Zhi-Jun
authors.initials: ZJ
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001921:Brain / Q000254:growth & development; D015283:Citalopram / Q000627:therapeutic use*; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D008297:Male; D008550:Melatonin / Q000235:genetics / Q000378:metabolism; D008569:Memory Disorders / Q000188:drug therapy* / Q000209:etiology; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D012934:Social Isolation; D065852:Spatial Memory; D013315:Stress, Psychological / Q000150:complications / Q000188:drug therapy*; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D015283:Citalopram; D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D008550:Melatonin; D017367:Selective Serotonin Reuptake Inhibitors; D016875:tau Proteins; C000605508:Gsk3b protein, rat