PMID- 28665013
OWN - NLM
STAT- MEDLINE
DCOM- 20180515
LR  - 20200930
IS  - 1474-9726 (Electronic)
IS  - 1474-9718 (Print)
IS  - 1474-9718 (Linking)
VI  - 16
IP  - 5
DP  - 2017 Oct
TI  - Epigenetic regulation by G9a/GLP complex ameliorates amyloid-beta 1-42 induced 
      deficits in long-term plasticity and synaptic tagging/capture in hippocampal 
      pyramidal neurons.
PG  - 1062-1072
LID - 10.1111/acel.12634 [doi]
AB  - Altered epigenetic mechanisms are implicated in the cognitive decline associated 
      with neurodegenerative diseases such as in Alzheimer's disease (AD). AD is the 
      most prevalent form of dementia worldwide; amyloid plaques and neurofibrillary 
      tangles are the histopathological hallmarks of AD. We have recently reported that 
      the inhibition of G9a/GLP complex promotes long-term potentiation (LTP) and its 
      associative mechanisms such as synaptic tagging and capture (STC). However, the 
      role of this complex in plasticity impairments remains elusive. Here, we 
      investigated the involvement of G9a/GLP complex in alleviating the effects of 
      soluble Amyloid-beta 1-42 oligomers (oAbeta) on neuronal plasticity and associativity 
      in the CA1 region of acute hippocampal slices from 5- to 7-week-old male Wistar 
      rats. Our findings demonstrate that the regulation of G9a/GLP complex by 
      inhibiting its catalytic activity reverses the amyloid-beta oligomer-induced 
      deficits in late-LTP and STC. This is achieved by releasing the transcription 
      repression of the brain-derived neurotrophic factor (Bdnf) gene. The catalytic 
      inhibition of G9a/GLP complex leads to the upregulation of Bdnf expression in the 
      slices treated with oAbeta. This further ensures the availability of BDNF that 
      subsequently binds its receptor tyrosine kinase B (TrkB) and maintains the 
      late-LTP. Furthermore, the capture of BDNF by weakly activated synapses 
      re-establishes STC. Our findings regarding the reinstatement of functional 
      plasticity and associativity in AD-like conditions provide the first evidence for 
      the role of G9a/GLP complex in AD. We propose G9a/GLP complex as the possible 
      target for preventing oAbeta-induced plasticity deficits in hippocampal neurons.
CI  - (c) 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley 
      & Sons Ltd.
FAU - Sharma, Mahima
AU  - Sharma M
AD  - Department of Physiology, Yong Loo Lin School of Medicine, National University of 
      Singapore, Block MD9, 2 Medical Drive, Singapore, 117 597, Singapore.
AD  - Neurobiology/Aging Program, Life Sciences Institute (LSI), National University of 
      Singapore, #04-44, 28 Medical Drive, Singapore, 117 456, Singapore.
FAU - Dierkes, Tobias
AU  - Dierkes T
AD  - Department of Physiology, Yong Loo Lin School of Medicine, National University of 
      Singapore, Block MD9, 2 Medical Drive, Singapore, 117 597, Singapore.
AD  - Institute of Innate Immunity, Biomedical Centre, University hospital Bonn, 
      Sigmund-Freud-Str. 25, Bonn, 53127, Germany.
AD  - Division of Cellular Neurobiology, Zoological Institute, Technical University 
      Braunschweig, Braunschweig, Germany.
FAU - Sajikumar, Sreedharan
AU  - Sajikumar S
AD  - Department of Physiology, Yong Loo Lin School of Medicine, National University of 
      Singapore, Block MD9, 2 Medical Drive, Singapore, 117 597, Singapore.
AD  - Neurobiology/Aging Program, Life Sciences Institute (LSI), National University of 
      Singapore, #04-44, 28 Medical Drive, Singapore, 117 456, Singapore.
LA  - eng
PT  - Journal Article
DEP - 20170630
PL  - England
TA  - Aging Cell
JT  - Aging cell
JID - 101130839
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Azepines)
RN  - 0 (BIX 01294)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Peptide Fragments)
RN  - 0 (Quinazolines)
RN  - 0 (UNC 0638)
RN  - 0 (amyloid beta-protein (1-42))
RN  - EC 2.1.1.43 (Ehmt2 protein, rat)
RN  - EC 2.1.1.43 (Histone-Lysine N-Methyltransferase)
RN  - EC 2.7.10.1 (Ntrk2 protein, rat)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
CIN - Aging (Albany NY). 2018 Jan 18;10(1):1-2. PMID: 29348393
MH  - Amyloid beta-Peptides/*antagonists & inhibitors/pharmacology
MH  - Animals
MH  - Azepines/pharmacology
MH  - Brain-Derived Neurotrophic Factor/genetics/metabolism
MH  - CA1 Region, Hippocampal/metabolism/pathology
MH  - Cognitive Dysfunction/chemically induced/genetics/physiopathology/*prevention & 
      control
MH  - *Epigenesis, Genetic
MH  - Histone-Lysine N-Methyltransferase/antagonists & inhibitors/*genetics/metabolism
MH  - Long-Term Potentiation/drug effects
MH  - Male
MH  - Microtomy
MH  - Peptide Fragments/*antagonists & inhibitors/pharmacology
MH  - Pyramidal Cells/*drug effects/metabolism/pathology
MH  - Quinazolines/pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Receptor, trkB/genetics/metabolism
MH  - Synapses/drug effects
MH  - Tissue Culture Techniques
PMC - PMC5595698
OTO - NOTNLM
OT  - BDNF
OT  - amyloid beta oligomer
OT  - epigenetics
OT  - histone lysine-methyltransferase
OT  - long-term potentiation
OT  - synaptic tagging/capture
EDAT- 2017/07/01 06:00
MHDA- 2018/05/16 06:00
PMCR- 2017/10/01
CRDT- 2017/07/01 06:00
PHST- 2017/05/27 00:00 [accepted]
PHST- 2017/07/01 06:00 [pubmed]
PHST- 2018/05/16 06:00 [medline]
PHST- 2017/07/01 06:00 [entrez]
PHST- 2017/10/01 00:00 [pmc-release]
AID - ACEL12634 [pii]
AID - 10.1111/acel.12634 [doi]
PST - ppublish
SO  - Aging Cell. 2017 Oct;16(5):1062-1072. doi: 10.1111/acel.12634. Epub 2017 Jun 30.