PMID- 25192638 OWN - NLM STAT- MEDLINE DCOM- 20150724 LR - 20200205 IS - 1872-7549 (Electronic) IS - 0166-4328 (Linking) VI - 275 DP - 2014 Dec 15 TI - Progressive alterations of hippocampal CA3-CA1 synapses in an animal model of depression. PG - 191-200 LID - S0166-4328(14)00552-X [pii] LID - 10.1016/j.bbr.2014.08.040 [doi] AB - 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. CI - Copyright (c) 2014 Elsevier B.V. All rights reserved. FAU - Qiao, Hui AU - Qiao H AD - College of Life Science, Shaanxi Normal University, Xi'an, Shaanxi Province 710062, PR China. FAU - An, Shu-Cheng AU - An SC AD - College of Life Science, Shaanxi Normal University, Xi'an, Shaanxi Province 710062, PR China. Electronic address: shuchengan@snnu.edu.cn. FAU - Ren, Wei AU - Ren W AD - College of Life Science, Shaanxi Normal University, Xi'an, Shaanxi Province 710062, PR China. FAU - Ma, Xin-Ming AU - Ma XM AD - 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. LA - eng GR - DA032973/DA/NIDA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20140901 PL - Netherlands TA - Behav Brain Res JT - Behavioural brain research JID - 8004872 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Guanine Nucleotide Exchange Factors) RN - 0 (Kalrn protein, rat) RN - 0 (Sweetening Agents) RN - 57-50-1 (Sucrose) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/metabolism MH - CA1 Region, Hippocampal/*pathology MH - CA3 Region, Hippocampal/*pathology MH - Depression/*pathology/physiopathology MH - Disease Models, Animal MH - Excitatory Postsynaptic Potentials/physiology MH - Exploratory Behavior MH - Food Preferences MH - Guanine Nucleotide Exchange Factors/metabolism MH - Hindlimb Suspension MH - Male MH - Maze Learning MH - Nerve Net/pathology/ultrastructure MH - Rats MH - Rats, Sprague-Dawley MH - Sucrose/administration & dosage MH - Sweetening Agents/administration & dosage MH - Synapses/*pathology/ultrastructure MH - Time Factors OTO - NOTNLM OT - BDNF OT - Dendritic spine OT - Kalirin OT - Stress OT - Synaptic plasticity EDAT- 2014/09/07 06:00 MHDA- 2015/07/25 06:00 CRDT- 2014/09/07 06:00 PHST- 2013/11/03 00:00 [received] PHST- 2014/08/08 00:00 [revised] PHST- 2014/08/20 00:00 [accepted] PHST- 2014/09/07 06:00 [entrez] PHST- 2014/09/07 06:00 [pubmed] PHST- 2015/07/25 06:00 [medline] AID - S0166-4328(14)00552-X [pii] AID - 10.1016/j.bbr.2014.08.040 [doi] PST - ppublish SO - Behav Brain Res. 2014 Dec 15;275:191-200. doi: 10.1016/j.bbr.2014.08.040. Epub 2014 Sep 1.