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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.
- Source :
-
Aging Cell . Oct2017, Vol. 16 Issue 5, p1062-1072. 11p. - Publication Year :
- 2017
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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-β 1-42 oligomers ( oAβ) 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-β 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 oAβ. 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 oAβ-induced plasticity deficits in hippocampal neurons. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 14749718
- Volume :
- 16
- Issue :
- 5
- Database :
- Academic Search Index
- Journal :
- Aging Cell
- Publication Type :
- Academic Journal
- Accession number :
- 125110515
- Full Text :
- https://doi.org/10.1111/acel.12634