期刊
EXPERIMENTAL NEUROBIOLOGY
卷 28, 期 4, 页码 537-546出版社
KOREAN SOC BRAIN & NEURAL SCIENCE, KOREAN SOC NEURODEGENERATIVE DISEASE
DOI: 10.5607/en.2019.28.4.537
关键词
SIRT2; depression; Ehmt2; Synaptic plasticity; Hippocampus
资金
- National Research Foundation of Korea (NRF) [2019R1A2C2003616]
- Medical Research Center [2017R1A5A2015395]
- Ministry of Science and Technology (MEST), Republic of Korea [2017R1A6A3A01005765]
- National Research Foundation of Korea [2019R1A2C2003616, 2017R1A6A3A01005765] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Silent information regulator 2 (Sirtuin2 / SIRT2) is a NAD(+)-dependent deacetylase that regulates the cellular oxidative stress response. It modulates transcriptional silencing and protein stability through deacetylation of target proteins including histones. Previous studies have shown that SIRT2 plays a role in mood disorders and hippocampus-dependent cognitive function, but the underlying neurobiological mechanism is poorly understood. Here, we report that chronic stress suppresses SIRT2 expression in the hippocampus. Molecular and biochemical analyses indicate that the stress-induced decrease in the SIRT2 expression downregulates synaptic plasticity-related genes in the hippocampus through the increase of euchromatic histone-lysine N-methyltransferase 2 (Ehmt2) (also known as G9a). shRNA-mediated knockdown of SIRT2 in the dentate gyrus alters the expression of synaptic plasticity-related genes in a way similar to those induced by chronic stress, and produces depression-like behaviors. Our results indicate that SIRT2 plays an important role in the response to stress, thereby modulating depression-like behaviors.
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