PMID- 30102916
OWN - NLM
STAT- MEDLINE
DCOM- 20190304
LR  - 20210109
IS  - 1090-2430 (Electronic)
IS  - 0014-4886 (Print)
IS  - 0014-4886 (Linking)
VI  - 309
DP  - 2018 Nov
TI  - Targeting histone deacetylation for recovery of maternal deprivation-induced 
      changes in BDNF and AKAP150 expression in the VTA.
PG  - 160-168
LID - S0014-4886(18)30336-4 [pii]
LID - 10.1016/j.expneurol.2018.08.002 [doi]
AB  - Severe early life stressors increase the probability of developing psychiatric 
      disorders later in life through modifications in neuronal circuits controlling 
      brain monoaminergic signaling. Our previous work demonstrated that 24 h maternal 
      deprivation (MD) in male Sprague Dawley rats modifies dopamine (DA) signaling 
      from the ventral tegmental area (VTA) through changes at GABAergic synapses that 
      were reversible by in vitro histone deacetylase (HDAC) inhibition which led to 
      restoration of the scaffold A-kinase anchoring protein (AKAP150) signaling and 
      subsequently recovered GABAergic plasticity (Authement et al., 2015). Using a 
      combination of in situ hybridization, Western blots and immunohistochemistry, we 
      confirmed that MD-induced epigenetic modifications at the level of histone 
      acetylation were associated with an upregulation of HDAC2. MD also increased 
      Akap5 mRNA levels in the VTA. Western blot analysis of AKAP150 protein expression 
      showed an increase in synaptic levels of AKAP150 protein in the VTA with an 
      accompanying decrease in synaptic levels of protein kinase A (PKA). Moreover, the 
      abundance of mature brain-derived neurotrophic factor (BDNF) protein of VTA 
      tissues from MD rats was significantly lower than in control groups. In vivo 
      systemic injection with a selective class I HDAC inhibitor (CI-994) was 
      sufficient to reverse MD-induced histone hypoacetylation in the VTA for 24 h 
      after the injection. Furthermore, HDAC inhibition normalized the levels of mBDNF 
      and AKAP150 proteins at 24 h. Our data suggest that HDAC-mediated targeting of 
      BDNF and AKAP-dependent local signaling within VTA could provide novel 
      therapeutics for prevention of later-life psychopathology.
CI  - Published by Elsevier Inc.
FAU - Shepard, Ryan D
AU  - Shepard RD
AD  - Uniformed Services University of the Health Sciences, Department of Pharmacology, 
      Bethesda, MD 20814, USA.
FAU - Gouty, Shawn
AU  - Gouty S
AD  - Uniformed Services University of the Health Sciences, Department of Pharmacology, 
      Bethesda, MD 20814, USA.
FAU - Kassis, Haifa
AU  - Kassis H
AD  - Uniformed Services University of the Health Sciences, Department of Pharmacology, 
      Bethesda, MD 20814, USA.
FAU - Berenji, Aylar
AU  - Berenji A
AD  - Uniformed Services University of the Health Sciences, Department of Pharmacology, 
      Bethesda, MD 20814, USA.
FAU - Zhu, William
AU  - Zhu W
AD  - Uniformed Services University of the Health Sciences, Department of Pharmacology, 
      Bethesda, MD 20814, USA.
FAU - Cox, Brian M
AU  - Cox BM
AD  - Uniformed Services University of the Health Sciences, Department of Pharmacology, 
      Bethesda, MD 20814, USA.
FAU - Nugent, Fereshteh S
AU  - Nugent FS
AD  - Uniformed Services University of the Health Sciences, Department of Pharmacology, 
      Bethesda, MD 20814, USA. Electronic address: fereshteh.nugent@usuhs.edu.
LA  - eng
GR  - R01 DA039533/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20180810
PL  - United States
TA  - Exp Neurol
JT  - Experimental neurology
JID - 0370712
RN  - 0 (A Kinase Anchor Proteins)
RN  - 0 (Akap5 protein, rat)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Histones)
RN  - 0 (RNA, Messenger)
RN  - EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
RN  - EC 3.5.1.98 (Hdac2 protein, rat)
RN  - EC 3.5.1.98 (Histone Deacetylase 2)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - A Kinase Anchor Proteins/*metabolism
MH  - Acetylation/drug effects
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Dopamine/metabolism
MH  - Enzyme Inhibitors/pharmacology
MH  - Gene Expression Regulation/*physiology
MH  - Histone Deacetylase 2/genetics/metabolism
MH  - Histones/*metabolism
MH  - In Vitro Techniques
MH  - Male
MH  - *Maternal Deprivation
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Subcellular Fractions/drug effects/metabolism
MH  - Tyrosine 3-Monooxygenase/metabolism
MH  - Ventral Tegmental Area/drug effects/*metabolism
PMC - PMC6139260
MID - NIHMS1504395
OTO - NOTNLM
OT  - A-kinase anchoring protein (AKAP)
OT  - Brain derived neurotrophic factor (BDNF)
OT  - Dopamine
OT  - Early life stress
OT  - Epigenetics
OT  - Histone acetylation
OT  - Histone deacetylase (HDAC)
OT  - Histone deacetylase inhibitor (HDAC inhibitor)
OT  - Maternal deprivation (MD)
OT  - Ventral tegmental area (VTA)
COIS- Declarations of interest: none.
EDAT- 2018/08/14 06:00
MHDA- 2019/03/05 06:00
PMCR- 2019/11/01
CRDT- 2018/08/14 06:00
PHST- 2018/04/04 00:00 [received]
PHST- 2018/07/17 00:00 [revised]
PHST- 2018/08/09 00:00 [accepted]
PHST- 2018/08/14 06:00 [pubmed]
PHST- 2019/03/05 06:00 [medline]
PHST- 2018/08/14 06:00 [entrez]
PHST- 2019/11/01 00:00 [pmc-release]
AID - S0014-4886(18)30336-4 [pii]
AID - 10.1016/j.expneurol.2018.08.002 [doi]
PST - ppublish
SO  - Exp Neurol. 2018 Nov;309:160-168. doi: 10.1016/j.expneurol.2018.08.002. Epub 2018 
      Aug 10.