title: Changed Synaptic Plasticity in Neural Circuits of Depressive-Like and Escitalopram-Treated Rats.
abstract: BACKGROUND
  Although progress has been made in the detection and characterization of neural plasticity in depression, it has not been fully understood in individual synaptic changes in the neural circuits under chronic stress and antidepressant treatment.
  
  
  METHODS
  Using electron microscopy and Western-blot analyses, the present study quantitatively examined the changes in the Gray's Type I synaptic ultrastructures and the expression of synapse-associated proteins in the key brain regions of rats' depressive-related neural circuit after chronic unpredicted mild stress and/or escitalopram administration. Meanwhile, their depressive behaviors were also determined by several tests.
  
  
  RESULTS
  The Type I synapses underwent considerable remodeling after chronic unpredicted mild stress, which resulted in the changed width of the synaptic cleft, length of the active zone, postsynaptic density thickness, and/or synaptic curvature in the subregions of medial prefrontal cortex and hippocampus, as well as the basolateral amygdaloid nucleus of the amygdala, accompanied by changed expression of several synapse-associated proteins. Chronic escitalopram administration significantly changed the above alternations in the chronic unpredicted mild stress rats but had little effect on normal controls. Also, there was a positive correlation between the locomotor activity and the maximal synaptic postsynaptic density thickness in the stratum radiatum of the Cornu Ammonis 1 region and a negative correlation between the sucrose preference and the length of the active zone in the basolateral amygdaloid nucleus region in chronic unpredicted mild stress rats.
  
  
  CONCLUSIONS
  These findings strongly indicate that chronic stress and escitalopram can alter synaptic plasticity in the neural circuits, and the remodeled synaptic ultrastructure was correlated with the rats' depressive behaviors, suggesting a therapeutic target for further exploration.
authors.affiliation: Department of Neurology, Affiliated ZhongDa Hospital, Neuropsychiatric Institute and Medical School of Southeast University, Nanjing, Jiangsu, China (Drs Li, Yuan, H. Xu, D. Wu, Gong, Geng, F-F. Wu, Tang, and Zhang); Key Laboratory of Animal Models and Human Disease Mechanisms, Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China (Dr L. Xu); Graduate School of Chinese Academy of Sciences, Beijing, China (Dr L. Xu)X-L.L. and Y-G.Y. contributed equally to this work.
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Li
authors.affiliation: Department of Neurology, Affiliated ZhongDa Hospital, Neuropsychiatric Institute and Medical School of Southeast University, Nanjing, Jiangsu, China (Drs Li, Yuan, H. Xu, D. Wu, Gong, Geng, F-F. Wu, Tang, and Zhang); Key Laboratory of Animal Models and Human Disease Mechanisms, Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China (Dr L. Xu); Graduate School of Chinese Academy of Sciences, Beijing, China (Dr L. Xu)X-L.L. and Y-G.Y. contributed equally to this work.
authors.forename: Yong-Gui
authors.initials: YG
authors.lastname: Yuan
authors.affiliation: Department of Neurology, Affiliated ZhongDa Hospital, Neuropsychiatric Institute and Medical School of Southeast University, Nanjing, Jiangsu, China (Drs Li, Yuan, H. Xu, D. Wu, Gong, Geng, F-F. Wu, Tang, and Zhang); Key Laboratory of Animal Models and Human Disease Mechanisms, Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China (Dr L. Xu); Graduate School of Chinese Academy of Sciences, Beijing, China (Dr L. Xu)X-L.L. and Y-G.Y. contributed equally to this work.
authors.forename: Hua
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Neurology, Affiliated ZhongDa Hospital, Neuropsychiatric Institute and Medical School of Southeast University, Nanjing, Jiangsu, China (Drs Li, Yuan, H. Xu, D. Wu, Gong, Geng, F-F. Wu, Tang, and Zhang); Key Laboratory of Animal Models and Human Disease Mechanisms, Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China (Dr L. Xu); Graduate School of Chinese Academy of Sciences, Beijing, China (Dr L. Xu)X-L.L. and Y-G.Y. contributed equally to this work.
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Neurology, Affiliated ZhongDa Hospital, Neuropsychiatric Institute and Medical School of Southeast University, Nanjing, Jiangsu, China (Drs Li, Yuan, H. Xu, D. Wu, Gong, Geng, F-F. Wu, Tang, and Zhang); Key Laboratory of Animal Models and Human Disease Mechanisms, Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China (Dr L. Xu); Graduate School of Chinese Academy of Sciences, Beijing, China (Dr L. Xu)X-L.L. and Y-G.Y. contributed equally to this work.
authors.forename: Wei-Gang
authors.initials: WG
authors.lastname: Gong
authors.affiliation: Department of Neurology, Affiliated ZhongDa Hospital, Neuropsychiatric Institute and Medical School of Southeast University, Nanjing, Jiangsu, China (Drs Li, Yuan, H. Xu, D. Wu, Gong, Geng, F-F. Wu, Tang, and Zhang); Key Laboratory of Animal Models and Human Disease Mechanisms, Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China (Dr L. Xu); Graduate School of Chinese Academy of Sciences, Beijing, China (Dr L. Xu)X-L.L. and Y-G.Y. contributed equally to this work.
authors.forename: Lei-Yu
authors.initials: LY
authors.lastname: Geng
authors.affiliation: Department of Neurology, Affiliated ZhongDa Hospital, Neuropsychiatric Institute and Medical School of Southeast University, Nanjing, Jiangsu, China (Drs Li, Yuan, H. Xu, D. Wu, Gong, Geng, F-F. Wu, Tang, and Zhang); Key Laboratory of Animal Models and Human Disease Mechanisms, Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China (Dr L. Xu); Graduate School of Chinese Academy of Sciences, Beijing, China (Dr L. Xu)X-L.L. and Y-G.Y. contributed equally to this work.
authors.forename: Fang-Fang
authors.initials: FF
authors.lastname: Wu
authors.affiliation: Department of Neurology, Affiliated ZhongDa Hospital, Neuropsychiatric Institute and Medical School of Southeast University, Nanjing, Jiangsu, China (Drs Li, Yuan, H. Xu, D. Wu, Gong, Geng, F-F. Wu, Tang, and Zhang); Key Laboratory of Animal Models and Human Disease Mechanisms, Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China (Dr L. Xu); Graduate School of Chinese Academy of Sciences, Beijing, China (Dr L. Xu)X-L.L. and Y-G.Y. contributed equally to this work.
authors.forename: Hao
authors.initials: H
authors.lastname: Tang
authors.affiliation: Department of Neurology, Affiliated ZhongDa Hospital, Neuropsychiatric Institute and Medical School of Southeast University, Nanjing, Jiangsu, China (Drs Li, Yuan, H. Xu, D. Wu, Gong, Geng, F-F. Wu, Tang, and Zhang); Key Laboratory of Animal Models and Human Disease Mechanisms, Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China (Dr L. Xu); Graduate School of Chinese Academy of Sciences, Beijing, China (Dr L. Xu)X-L.L. and Y-G.Y. contributed equally to this work.
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Neurology, Affiliated ZhongDa Hospital, Neuropsychiatric Institute and Medical School of Southeast University, Nanjing, Jiangsu, China (Drs Li, Yuan, H. Xu, D. Wu, Gong, Geng, F-F. Wu, Tang, and Zhang); Key Laboratory of Animal Models and Human Disease Mechanisms, Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China (Dr L. Xu); Graduate School of Chinese Academy of Sciences, Beijing, China (Dr L. Xu)X-L.L. and Y-G.Y. contributed equally to this work. janemengzhang@vip.163.com.
authors.forename: Zhi-Jun
authors.initials: ZJ
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology / Q000648:ultrastructure; D002908:Chronic Disease; D015283:Citalopram / Q000494:pharmacology*; D003866:Depressive Disorder / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D019422:Dietary Sucrose / Q000008:administration & dosage; D004195:Disease Models, Animal; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology; D008297:Male; D008854:Microscopy, Electron; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects / Q000503:physiopathology / Q000648:ultrastructure; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D011581:Psychological Tests; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological; D013569:Synapses / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D035501:Uncertainty
chemical_list: D000928:Antidepressive Agents; D019422:Dietary Sucrose; D015283:Citalopram
keywords: Synapse; depression; plasticity; rat