Please use this identifier to cite or link to this item: https://doi.org/10.1111/acel.12634
Title: 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
Authors: Sharma, M 
Dierkes, T
Sajikumar, S 
Keywords: amyloid beta protein[1-42]
brain derived neurotrophic factor
brain derived neurotrophic factor receptor
G9a GLP complex
histone lysine methyltransferase
unclassified drug
2 cyclohexyl n (1 isopropyl 4 piperidinyl) 6 methoxy 7 [3 (1 pyrrolidinyl)propoxy] 4 quinazolinamine
amyloid beta protein
amyloid beta-protein (1-42)
azepine derivative
brain derived neurotrophic factor
brain derived neurotrophic factor receptor
G9a protein, rat
histone lysine methyltransferase
n (1 benzyl 4 piperidinyl) 2 (hexahydro 4 methyl 1h 1,4 diazepin 1 yl) 6,7 dimethoxy 4 quinazolinamine
peptide fragment
quinazoline derivative
TrkB protein, rat
adult
Alzheimer disease
animal tissue
Article
catalysis
controlled study
epigenetic repression
gene expression
hippocampal CA1 region
hippocampal slice
long term potentiation
male
nerve cell plasticity
nonhuman
priority journal
pyramidal nerve cell
rat
synaptic tagging and capture
synaptic transmission
upregulation
animal
antagonists and inhibitors
chemically induced
cognitive defect
drug effect
genetic epigenesis
genetics
hippocampal CA1 region
long term potentiation
metabolism
microtomy
pathology
pathophysiology
synapse
tissue culture technique
Wistar rat
Amyloid beta-Peptides
Animals
Azepines
Brain-Derived Neurotrophic Factor
CA1 Region, Hippocampal
Cognitive Dysfunction
Epigenesis, Genetic
Histone-Lysine N-Methyltransferase
Long-Term Potentiation
Male
Microtomy
Peptide Fragments
Pyramidal Cells
Quinazolines
Rats
Rats, Wistar
Receptor, trkB
Synapses
Tissue Culture Techniques
Issue Date: 2017
Citation: Sharma, M, Dierkes, T, Sajikumar, S (2017). 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. Aging Cell 16 (5) : 1062-1072. ScholarBank@NUS Repository. https://doi.org/10.1111/acel.12634
Abstract: 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-? 1-42 oligomers (oA?) 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-? 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 oA?. 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 oA?-induced plasticity deficits in hippocampal neurons. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
Source Title: Aging Cell
URI: https://scholarbank.nus.edu.sg/handle/10635/175424
ISSN: 1474-9718
DOI: 10.1111/acel.12634
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