title: Progressive alterations of hippocampal CA3-CA1 synapses in an animal model of depression.
abstract: Major depressive disorder is the most prevalent psychiatric condition, but the cellular and molecular mechanisms underlying this disorder are largely unknown, although multiple hypotheses have been proposed. The aim of this study was to characterize the progressive alteration of neuronal plasticity in the male rat hippocampus during depression induced by chronic unpredictable mild stress (CUMS), an established animal model of depression. The data in the hippocampus were collected on days 7, 14 and 21 after the onset of three-week CUMS. When analyzed on day 21, three-week CUMS induced typically depressive-like behaviors, impaired LTP induction, and decreased basal synaptic transmission at hippocampal CA3-CA1 synapses recorded in vivo, which was accompanied by decreased density of dendritic spines in CA1 and CA3 pyramidal neurons. The levels of both Kalirin-7 and brain-derived neurotrophic factor (BDNF) in the hippocampus were decreased at the same time. On day 14 (middle phase), some depressive-like behaviors were observed, which was accompanied by depressed basal synaptic transmission and enhanced LTP induction at the CA3-CA1 synapses. However, BDNF expression was decreased without alteration of Kalirin7 expression in comparison with no-stress control. Depressed basal synaptic transmission occurred in the middle phase of CUMS may contribute to decreased expression of BDNF. On day 7, depressive-like behaviors were not observed, and LTP induction, spine density, Kalirin-7 and BDNF expression were not altered by CUMS in comparison with no-stress control. These results showed that the functional changes at CA3-CA1synapses occurred earlier than the structural alteration during three-week CUMS as a strategy of neural adaptation, and rats required three weeks to develop depressive-like behaviors during CUMS. Our results suggest an important role of Kalirin-7 in CUMS-mediated alterations in spine density, synaptic function and overall depressive-like behaviors on day 21.
authors.affiliation: College of Life Science, Shaanxi Normal University, Xi'an, Shaanxi Province 710062, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Qiao
authors.affiliation: College of Life Science, Shaanxi Normal University, Xi'an, Shaanxi Province 710062, PR China. Electronic address: shuchengan@snnu.edu.cn.
authors.forename: Shu-Cheng
authors.initials: SC
authors.lastname: An
authors.affiliation: College of Life Science, Shaanxi Normal University, Xi'an, Shaanxi Province 710062, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ren
authors.affiliation: College of Life Science, Shaanxi Normal University, Xi'an, Shaanxi Province 710062, PR China; University of Connecticut Health Center, Department of Neuroscience, Farmington, CT 06030, USA.
authors.forename: Xin-Ming
authors.initials: XM
authors.lastname: Ma
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D056547:CA1 Region, Hippocampal / Q000473:pathology*; D056654:CA3 Region, Hippocampal / Q000473:pathology*; D003863:Depression / Q000473:pathology* / Q000503:physiopathology; D004195:Disease Models, Animal; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005106:Exploratory Behavior; D005518:Food Preferences; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D019417:Hindlimb Suspension; D008297:Male; D018782:Maze Learning; D009415:Nerve Net / Q000473:pathology / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D013395:Sucrose / Q000008:administration & dosage; D013549:Sweetening Agents / Q000008:administration & dosage; D013569:Synapses / Q000473:pathology* / Q000648:ultrastructure; D013997:Time Factors
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D020662:Guanine Nucleotide Exchange Factors; C102365:Kalrn protein, rat; D013549:Sweetening Agents; D013395:Sucrose
keywords: BDNF; Dendritic spine; Kalirin; Stress; Synaptic plasticity