PMID- 24204683
OWN - NLM
STAT- MEDLINE
DCOM- 20140826
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 10
DP  - 2013
TI  - Induction of DARPP-32 by brain-derived neurotrophic factor in striatal neurons in 
      vitro is modified by histone deacetylase inhibitors and Nab2.
PG  - e76842
LID - 10.1371/journal.pone.0076842 [doi]
LID - e76842
AB  - Neurotrophins and modifiers of chromatin acetylation and deacetylation 
      participate in regulation of transcription during neuronal maturation and 
      maintenance. The striatal medium spiny neuron is supported by cortically-derived 
      brain derived neurotrophic factor and is the most vulnerable neuron in 
      Huntington's disease, in which growth factor and histone deacetylase activity are 
      both disrupted. We examined the ability of three histone deacetylase inhibitors, 
      trichostatin A, valproic acid and Compound 4 b, alone and combined with brain 
      derived neurotrophic factor (BDNF), to promote phenotypic maturation of striatal 
      medium spiny neurons in vitro. Exposure of these neurons to each of the three 
      compounds led to an increase in overall histone H3 and H4 acetylation, dopamine 
      and cyclic AMP-regulated phosphoprotein, 32 kDa (DARPP-32) mRNA and protein, and 
      mRNA levels of other markers of medium spiny neuron maturation. We were, however, 
      unable to prove that HDAC inhibitors directly lead to remodeling of Ppp1r1b 
      chromatin. In addition, induction of DARPP-32 by brain-derived neurotrophic 
      factor was inhibited by histone deacetylase inhibitors. Although BDNF-induced 
      increases in pTrkB, pAkt, pERK and Egr-1 were unchanged by combined application 
      with VPA, the increase in DARPP-32 was relatively diminished. Strikingly, the 
      NGF1A-binding protein, Nab2, was induced by BDNF, but not in the presence of VPA 
      or TSA. Gel shift analysis showed that alpha-Nab2 super-shifted a band that is more 
      prominent with extract derived from BDNF-treated neurons than with extracts from 
      cultures treated with VPA alone or VPA plus BDNF. In addition, overexpression of 
      Nab2 induced DARPP-32. We conclude that histone deacetylase inhibitors inhibit 
      the induction of Nab2 by BDNF, and thereby the relative induction of DARPP-32.
FAU - Chandwani, Samira
AU  - Chandwani S
AD  - Departments of Neurology and Pediatrics, Mount Sinai School of Medicine, New 
      York, New York, United States of America.
FAU - Keilani, Serene
AU  - Keilani S
FAU - Ortiz-Virumbrales, Maitane
AU  - Ortiz-Virumbrales M
FAU - Morant, Andrika
AU  - Morant A
FAU - Bezdecny, Steve
AU  - Bezdecny S
FAU - Ehrlich, Michelle E
AU  - Ehrlich ME
LA  - eng
GR  - R01 NS045942/NS/NINDS NIH HHS/United States
GR  - R01 NS059936/NS/NINDS NIH HHS/United States
GR  - NS-045942/NS/NINDS NIH HHS/United States
GR  - NS-059936/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20131021
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Bcl11b protein, mouse)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Calbindins)
RN  - 0 (Dopamine and cAMP-Regulated Phosphoprotein 32)
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - 0 (Histones)
RN  - 0 (Hydroxamic Acids)
RN  - 0 (Nab2 protein, mouse)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Ppp1r1b protein, mouse)
RN  - 0 (Repressor Proteins)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 3X2S926L3Z (trichostatin A)
RN  - 614OI1Z5WI (Valproic Acid)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
MH  - Acetylation/drug effects
MH  - Animals
MH  - Blotting, Western
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Calbindins/genetics/metabolism
MH  - Cell Differentiation/drug effects/genetics
MH  - Cells, Cultured
MH  - Corpus Striatum/cytology/drug effects/metabolism
MH  - Dopamine and cAMP-Regulated Phosphoprotein 32/genetics/*metabolism
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Histone Deacetylase Inhibitors/*pharmacology
MH  - Histones/metabolism
MH  - Hydroxamic Acids/pharmacology
MH  - Mice
MH  - NIH 3T3 Cells
MH  - Neoplasm Proteins/genetics/*metabolism
MH  - Neurons/*drug effects/metabolism
MH  - Phosphorylation/drug effects
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Receptor, trkB/metabolism
MH  - Repressor Proteins/genetics/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Tumor Suppressor Proteins/genetics/metabolism
MH  - Valproic Acid/pharmacology
PMC - PMC3804529
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/11/10 06:00
MHDA- 2014/08/27 06:00
PMCR- 2013/10/21
CRDT- 2013/11/09 06:00
PHST- 2012/12/23 00:00 [received]
PHST- 2013/08/29 00:00 [accepted]
PHST- 2013/11/09 06:00 [entrez]
PHST- 2013/11/10 06:00 [pubmed]
PHST- 2014/08/27 06:00 [medline]
PHST- 2013/10/21 00:00 [pmc-release]
AID - PONE-D-12-40714 [pii]
AID - 10.1371/journal.pone.0076842 [doi]
PST - epublish
SO  - PLoS One. 2013 Oct 21;8(10):e76842. doi: 10.1371/journal.pone.0076842. 
      eCollection 2013.