PMID- 25242807
OWN - NLM
STAT- MEDLINE
DCOM- 20151109
LR  - 20141202
IS  - 1873-5177 (Electronic)
IS  - 0091-3057 (Linking)
VI  - 126
DP  - 2014 Nov
TI  - Epigenetic suppression of hippocampal BDNF mediates the memory deficiency induced 
      by amyloid fibrils.
PG  - 83-9
LID - S0091-3057(14)00261-5 [pii]
LID - 10.1016/j.pbb.2014.09.009 [doi]
AB  - Accumulating evidences demonstrated that epigenetic modification of the 
      expression of specific genes contributed to the pathogenesis of neurological 
      disorders with dementia, including Alzheimer's disease (AD). Emerging reports 
      also found the reduction of hippocampal brain-derived neurotrophic factor (BDNF) 
      in the patients and rodent models of AD, while the mechanism and functional 
      significance remain debated. The present study aims to study the epigenetic 
      mechanism underlying the BDNF reduction and its functional significance in the 
      rats with hippocampal infusion of amyloid fibrils. In the rats injected with 
      amyloid fibrils, significant decreases of BDNF expression and the mRNA of Bdnf 
      exon VI were found in the hippocampal CA1 area. Significantly increased 
      hippocampal HDAC2 expression and its occupancy in the promoter region of Bdnf 
      exon VI were also observed, thus contributing to the histone H3 deacetylation and 
      BDNF suppression in the hippocampal CA1 in the rats injected with amyloid 
      fibrils. Inhibition of HDAC2 activity by trichostatin A substantially recovered 
      the histone H3 acetylation in the promoter region of Bdnf exon VI and BDNF 
      expression, thus mitigating the synaptic dysfunction and memory deficiency 
      induced by amyloid fibrils. These results elucidate the epigenetic mechanism 
      underlying the BDNF reduction induced by amyloid fibrils, and provided novel 
      insights into the pathogenic mechanism of Alzheimer's disease.
CI  - Copyright (c) 2014 Elsevier Inc. All rights reserved.
FAU - Wang, Bei-Yun
AU  - Wang BY
AD  - Department of Geriatrics, The Sixth People's Hospital affiliated to Shanghai Jiao 
      Tong University, Shanghai 200233, China.
FAU - Zhong, Yuan
AU  - Zhong Y
AD  - Department of Geriatrics, The Sixth People's Hospital affiliated to Shanghai Jiao 
      Tong University, Shanghai 200233, China. Electronic address: 
      zhongyuansh01@163.com.
FAU - Zhao, Zhe
AU  - Zhao Z
AD  - Department of Geriatrics, The Sixth People's Hospital affiliated to Shanghai Jiao 
      Tong University, Shanghai 200233, China.
FAU - Miao, Ya
AU  - Miao Y
AD  - Department of Geriatrics, The Sixth People's Hospital affiliated to Shanghai Jiao 
      Tong University, Shanghai 200233, China.
LA  - eng
PT  - Journal Article
DEP - 20140919
PL  - United States
TA  - Pharmacol Biochem Behav
JT  - Pharmacology, biochemistry, and behavior
JID - 0367050
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Histones)
RN  - 0 (Hydroxamic Acids)
RN  - 0 (Peptide Fragments)
RN  - 0 (amyloid beta-protein (1-42))
RN  - 3X2S926L3Z (trichostatin A)
RN  - EC 3.5.1.98 (Histone Deacetylase 2)
SB  - IM
MH  - Acetylation/drug effects
MH  - Amyloid beta-Peptides/administration & dosage/antagonists & inhibitors/*toxicity
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/biosynthesis/*genetics
MH  - CA1 Region, Hippocampal/*drug effects/*metabolism/physiology
MH  - Epigenesis, Genetic/*drug effects
MH  - Excitatory Postsynaptic Potentials/drug effects
MH  - Exploratory Behavior/drug effects
MH  - Histone Deacetylase 2/antagonists & inhibitors/biosynthesis
MH  - Histones/metabolism
MH  - Hydroxamic Acids/pharmacology
MH  - Male
MH  - Maze Learning/drug effects
MH  - Memory/*drug effects
MH  - Peptide Fragments/administration & dosage/antagonists & 
      inhibitors/pharmacology/*toxicity
MH  - Promoter Regions, Genetic/drug effects
MH  - Rats
OTO - NOTNLM
OT  - Amyloid fibrils
OT  - Brain-derived neurotrophic factor
OT  - Histone deacetylase 2
OT  - Memory
OT  - Synaptic plasticity
EDAT- 2014/09/23 06:00
MHDA- 2015/11/10 06:00
CRDT- 2014/09/23 06:00
PHST- 2014/03/20 00:00 [received]
PHST- 2014/09/07 00:00 [revised]
PHST- 2014/09/13 00:00 [accepted]
PHST- 2014/09/23 06:00 [entrez]
PHST- 2014/09/23 06:00 [pubmed]
PHST- 2015/11/10 06:00 [medline]
AID - S0091-3057(14)00261-5 [pii]
AID - 10.1016/j.pbb.2014.09.009 [doi]
PST - ppublish
SO  - Pharmacol Biochem Behav. 2014 Nov;126:83-9. doi: 10.1016/j.pbb.2014.09.009. Epub 
      2014 Sep 19.