PMID- 24636513
OWN - NLM
STAT- MEDLINE
DCOM- 20141107
LR  - 20220309
IS  - 1873-3360 (Electronic)
IS  - 0306-4530 (Print)
IS  - 0306-4530 (Linking)
VI  - 42
DP  - 2014 Apr
TI  - Glucocorticoid receptor activation impairs hippocampal plasticity by suppressing 
      BDNF expression in obese mice.
PG  - 165-77
LID - S0306-4530(14)00045-6 [pii]
LID - 10.1016/j.psyneuen.2014.01.020 [doi]
AB  - Diabetes and obesity are associated with perturbation of adrenal steroid hormones 
      and impairment of hippocampal plasticity, but the question of whether these 
      conditions recruit glucocorticoid-mediated molecular cascades that are comparable 
      to other stressors has yet to be fully addressed. We have used a genetic mouse 
      model of obesity and diabetes with chronically elevated glucocorticoids to 
      determine the mechanism for glucocorticoid-induced deficits in hippocampal 
      synaptic function. Pharmacological inhibition of adrenal steroidogenesis 
      attenuates structural and functional impairments by regulating plasticity among 
      dendritic spines in the hippocampus of leptin receptor deficient (db/db) mice. 
      Synaptic deficits evoked by exposure to elevated corticosterone levels in db/db 
      mice are attributable to glucocorticoid receptor-mediated transrepression of AP-1 
      actions at BDNF promoters I and IV. db/db mice exhibit corticosterone-mediated 
      reductions in brain-derived neurotrophic factor (BDNF), and a change in the ratio 
      of TrkB to P75NTR that silences the functional response to BDNF stimulation. 
      Lentiviral suppression of glucocorticoid receptor expression rescues behavioral 
      and synaptic function in db/db mice, and also reinstates BDNF expression, 
      underscoring the relevance of molecular mechanisms previously demonstrated after 
      psychological stress to the functional alterations observed in obesity and 
      diabetes.
CI  - Copyright (c) 2014 Elsevier Ltd. All rights reserved.
FAU - Wosiski-Kuhn, Marlena
AU  - Wosiski-Kuhn M
AD  - Department of Physiology, Medical College of Georgia, Georgia Regents University, 
      1120 15th Street, Augusta, GA 30912, USA.
FAU - Erion, Joanna R
AU  - Erion JR
AD  - Department of Physiology, Medical College of Georgia, Georgia Regents University, 
      1120 15th Street, Augusta, GA 30912, USA.
FAU - Gomez-Sanchez, Elise P
AU  - Gomez-Sanchez EP
AD  - G.V. (Sonny) Montgomery Veteran's Affairs Medical Center, 1500 Woodrow Wilson 
      Drive, Jackson, Jackson, MS 39216, USA.
FAU - Gomez-Sanchez, Celso E
AU  - Gomez-Sanchez CE
AD  - G.V. (Sonny) Montgomery Veteran's Affairs Medical Center, 1500 Woodrow Wilson 
      Drive, Jackson, Jackson, MS 39216, USA.
FAU - Stranahan, Alexis M
AU  - Stranahan AM
AD  - Department of Physiology, Medical College of Georgia, Georgia Regents University, 
      1120 15th Street, Augusta, GA 30912, USA. Electronic address: astranahan@gru.edu.
LA  - eng
GR  - R03 DK101817/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140130
PL  - England
TA  - Psychoneuroendocrinology
JT  - Psychoneuroendocrinology
JID - 7612148
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Receptors, Glucocorticoid)
RN  - EC 1.14.15.4 (Steroid 11-beta-Hydroxylase)
RN  - ZS9KD92H6V (Metyrapone)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/genetics/*metabolism
MH  - Enzyme Inhibitors/pharmacology
MH  - Hippocampus/drug effects/*metabolism
MH  - Metyrapone/pharmacology
MH  - Mice
MH  - Mice, Obese
MH  - Neuronal Plasticity/drug effects/*physiology
MH  - Receptors, Glucocorticoid/*metabolism
MH  - Steroid 11-beta-Hydroxylase/antagonists & inhibitors
PMC - PMC4426342
MID - NIHMS687259
OTO - NOTNLM
OT  - Corticosterone
OT  - Dendritic spine
OT  - Dentate gyrus
OT  - Hippocampus
OT  - Long-term potentiation
OT  - Synapse
OT  - Synaptic plasticity
EDAT- 2014/03/19 06:00
MHDA- 2014/11/08 06:00
PMCR- 2015/05/11
CRDT- 2014/03/19 06:00
PHST- 2013/10/11 00:00 [received]
PHST- 2014/01/21 00:00 [revised]
PHST- 2014/01/22 00:00 [accepted]
PHST- 2014/03/19 06:00 [entrez]
PHST- 2014/03/19 06:00 [pubmed]
PHST- 2014/11/08 06:00 [medline]
PHST- 2015/05/11 00:00 [pmc-release]
AID - S0306-4530(14)00045-6 [pii]
AID - 10.1016/j.psyneuen.2014.01.020 [doi]
PST - ppublish
SO  - Psychoneuroendocrinology. 2014 Apr;42:165-77. doi: 
      10.1016/j.psyneuen.2014.01.020. Epub 2014 Jan 30.