Depression and Social Defeat Stress Are Associated with Inhibitory Synaptic Changes in the Nucleus Accumbens.
depression
inhibitory synapse
nucleus accumbens
social defeat
stress
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
ISSN: 1529-2401
Titre abrégé: J Neurosci
Pays: United States
ID NLM: 8102140
Informations de publication
Date de publication:
05 08 2020
05 08 2020
Historique:
received:
28
10
2019
revised:
28
01
2020
accepted:
03
03
2020
pubmed:
21
6
2020
medline:
5
1
2021
entrez:
21
6
2020
Statut:
ppublish
Résumé
Chronic stress in both humans and rodents induces a robust downregulation of neuroligin-2, a key component of the inhibitory synapse, in the NAc that modifies behavioral coping mechanisms and stress resiliency in mice. Here we extend this observation by examining the role of two other inhibitory synapse constituents, vesicular GABA transporter (vGAT) and gephyrin, in the NAc of male mice that underwent chronic social defeat stress (CSDS) and in patients with major depressive disorder (MDD). We first performed transcriptional profiling of vGAT and gephyrin in postmortem NAc samples from a cohort of healthy controls, medicated, and nonmedicated MDD patients. In parallel, we conducted whole-cell electrophysiology recordings in the NAc of stress-susceptible and stress-resilient male mice following 10 d of CSDS. Finally, we used immunohistochemistry to analyze protein levels of vGAT and gephyrin in the NAc of mice after CSDS. We found that decreased vGAT and gephyrin mRNA in the NAc of nonmedicated MDD patients is paralleled by decreased inhibitory synapse markers and decreased frequency of mini inhibitory postsynaptic currents (mIPSC) in the NAc of susceptible mice, indicating a reduction in the number of NAc inhibitory synapses that is correlated with depression-like behavior. Overall, these findings suggest a common state of reduced inhibitory tone in the NAc in depression and stress susceptibility.
Identifiants
pubmed: 32561672
pii: JNEUROSCI.2568-19.2020
doi: 10.1523/JNEUROSCI.2568-19.2020
pmc: PMC7406280
doi:
Substances chimiques
Membrane Proteins
0
Vesicular Inhibitory Amino Acid Transport Proteins
0
gephyrin
0
vesicular GABA transporter
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
6228-6233Subventions
Organisme : NIMH NIH HHS
ID : R01 MH104559
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH120637
Pays : United States
Organisme : NCCIH NIH HHS
ID : P50 AT008661
Pays : United States
Organisme : NIMH NIH HHS
ID : R56 MH115409
Pays : United States
Organisme : NIMH NIH HHS
ID : F30 MH100835
Pays : United States
Organisme : NIMH NIH HHS
ID : T32 MH087004
Pays : United States
Organisme : NIMH NIH HHS
ID : P50 MH096890
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH114882
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH090264
Pays : United States
Informations de copyright
Copyright © 2020 the authors.
Références
Neuropsychopharmacology. 2018 May;43(6):1276-1283
pubmed: 29090682
Biol Psychiatry. 2014 Aug 1;76(3):231-8
pubmed: 24239130
Sci Rep. 2017 Oct 9;7(1):12838
pubmed: 28993631
Proc Natl Acad Sci U S A. 2018 Jan 30;115(5):1111-1116
pubmed: 29339486
Nat Neurosci. 2015 Jul;18(7):962-4
pubmed: 26030846
Biol Psychiatry. 2015 Feb 1;77(3):212-222
pubmed: 25173629
Mol Psychiatry. 2019 Dec;24(12):1798-1815
pubmed: 30967681
J Neurosci. 2013 Aug 28;33(35):14075-86
pubmed: 23986243
J Neurosci. 2010 Feb 10;30(6):2223-34
pubmed: 20147549
J Neurosci. 2015 Dec 16;35(50):16362-76
pubmed: 26674863
Nat Med. 2013 Mar;19(3):337-44
pubmed: 23416703
Neuroscience. 2018 Apr 15;376:108-116
pubmed: 29476894
Nat Protoc. 2011 Jul 21;6(8):1183-91
pubmed: 21799487
Science. 2006 Feb 10;311(5762):864-8
pubmed: 16469931
Neuroscience. 2020 Jul 15;439:125-136
pubmed: 31356900
Trends Neurosci. 1995 Dec;18(12):527-35
pubmed: 8638293
Neuropsychopharmacology. 2019 Dec;44(13):2220-2229
pubmed: 31493767
J Neurosci. 2011 Jul 20;31(29):10481-93
pubmed: 21775594
Neuron. 2012 Mar 22;73(6):1184-94
pubmed: 22445345
Cell. 2007 Oct 19;131(2):391-404
pubmed: 17956738
J Neurosci. 2008 May 21;28(21):5504-12
pubmed: 18495884
Nat Rev Neurosci. 2013 Sep;14(9):609-25
pubmed: 23942470
J Neurosci. 1998 Dec 1;18(23):9733-50
pubmed: 9822734
Nature. 2014 Dec 4;516(7529):51-5
pubmed: 25383518
Neuroscience. 2017 May 14;350:180-189
pubmed: 28323008
J Neurosci. 2011 Jan 5;31(1):314-21
pubmed: 21209217
Biol Psychiatry. 2019 Nov 1;86(9):657-668
pubmed: 31255250
Nat Rev Neurosci. 2014 Mar;15(3):141-56
pubmed: 24552784