PMID- 27260837
OWN - NLM
STAT- MEDLINE
DCOM- 20180227
LR  - 20181113
IS  - 1095-953X (Electronic)
IS  - 0969-9961 (Print)
IS  - 0969-9961 (Linking)
VI  - 94
DP  - 2016 Oct
TI  - Cognitive deficits triggered by early life stress: The role of histone 
      deacetylase 1.
PG  - 1-9
LID - S0969-9961(16)30120-6 [pii]
LID - 10.1016/j.nbd.2016.05.018 [doi]
AB  - Studies showed that histone deacetylase (HDAC) inhibitors can reverse cognitive 
      deficits found in neurodegenerative disorders and age-related memory decline. 
      However, the role of HDACs in stress-induced cognitive deficits has not been 
      investigated. In the stress-susceptible mouse strain Balb/c, early life stress 
      triggers a persistent decrease in HDAC expression in the forebrain neocortex, 
      including reduced expression of class I HDACs. The same mice show pronounced 
      cognitive deficits in adulthood, namely deficits in working memory and attention 
      set-shifting. Here we show that these mice also exhibit reduced association of 
      HDAC1 with promotor III of the brain-derived neurotrophic factor (Bdnf) gene, and 
      that cognitive testing leads to abnormally increased Bdnf mRNA expression. A 
      pharmacological reduction of Bdnf-tropomyosine kinase B receptor signaling 
      effectively reverses the cognitive deficits, indicating that enhanced 
      transcriptional activation of the Bdnf gene contributes to their emergence. In 
      contrast to Balb/c mice, C57Bl/6 mice only develop attention set-shifting 
      deficits when raised by Balb/c foster mothers during the time the pups are 
      exposed to early life stress. HDAC1 levels at Bdnf promotor III are unaltered in 
      such C57Bl/6 mice, although they exhibit decreased levels of HDAC1 at the 
      promotor of the early-growth response gene 2 (Egr2) and abnormally increased Egr2 
      mRNA expression after cognitive testing. Hence, contrary to the beneficial 
      effects of HDAC inhibition in neurodegenerative diseases, the reduced HDAC1 
      levels at promotors of distinct plasticity-associated genes predispose animals 
      exposed to early life stress to enhanced expression of these genes upon cognitive 
      challenge, an effect that negatively influences cognitive task performance.
CI  - Copyright (c) 2016 Elsevier Inc. All rights reserved.
FAU - Adler, Samantha M
AU  - Adler SM
AD  - Department of Psychiatry, Columbia University, New York, NY 10032, United States.
FAU - Schmauss, Claudia
AU  - Schmauss C
AD  - Department of Psychiatry, Columbia University, New York, NY 10032, United States; 
      Division of Molecular Therapeutics, New York State Psychiatric Institute, New 
      York, NY 10032, United States. Electronic address: cs581@cumc.columbia.edu.
LA  - eng
GR  - R21 MH099251/MH/NIMH NIH HHS/United States
PT  - Journal Article
DEP - 20160531
PL  - United States
TA  - Neurobiol Dis
JT  - Neurobiology of disease
JID - 9500169
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 3.5.1.98 (Hdac1 protein, mouse)
RN  - EC 3.5.1.98 (Histone Deacetylase 1)
SB  - IM
MH  - Animals
MH  - Cognition/*physiology
MH  - Cognition Disorders/genetics/*physiopathology
MH  - Cognitive Dysfunction/genetics/*physiopathology
MH  - Histone Deacetylase 1/genetics/*metabolism
MH  - Histone Deacetylase Inhibitors/pharmacology
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Neurons/metabolism
MH  - Receptor, trkB/metabolism
MH  - Stress, Physiological/genetics/*physiology
PMC - PMC4983517
MID - NIHMS793261
OTO - NOTNLM
OT  - Attention set-shifting
OT  - Bdnf promotor
OT  - Egr2 promotor
OT  - Gene expression
OT  - HDAC1 activity
OT  - Working memory
COIS- CONFLICT OF INTEREST: The authors declare no competing financial interest.
EDAT- 2016/06/05 06:00
MHDA- 2018/02/28 06:00
PMCR- 2017/10/01
CRDT- 2016/06/05 06:00
PHST- 2015/12/30 00:00 [received]
PHST- 2016/05/13 00:00 [revised]
PHST- 2016/05/30 00:00 [accepted]
PHST- 2016/06/05 06:00 [entrez]
PHST- 2016/06/05 06:00 [pubmed]
PHST- 2018/02/28 06:00 [medline]
PHST- 2017/10/01 00:00 [pmc-release]
AID - S0969-9961(16)30120-6 [pii]
AID - 10.1016/j.nbd.2016.05.018 [doi]
PST - ppublish
SO  - Neurobiol Dis. 2016 Oct;94:1-9. doi: 10.1016/j.nbd.2016.05.018. Epub 2016 May 31.