Pharmacological Inhibition of the G9a/GLP Histone Methyltransferase and Anxiety-related Behaviour in the Mouse
Year: 2016
Type: dissertation
Abstract: Anxiety disorders are the most prevalent category of psychiatric diagnosis and are one of the leading causes of disability in developed countries. Several existing antidepressants with anti-anxiety properties have been shown to downregulate G9a, a methyltransferase that methylates lysine 9 of histone H3 (H3K9). Histone methylation regulates epigenetic responses to environmental stress. Thus we sought to investigate the role of G9a/GLP in regulating anxiety behaviour during adulthood and neurodevelopment. C57BL/6 mice were treated with G9a/GLP inhibitors, UNC0642 and A-366, at doses of 1mg/kg, 2mg/kg or 4mg/kg. In adult mice, both drugs decreased anxiety-related behaviours. Inhibition of G9a/GLP in utero increased anxiety-like behaviours and decreased social interaction in adulthood. These findings suggest that G9a/GLP inhibition has the potential to alleviate anxiety symptoms and could be pursued as a novel anti-anxiety drug target. Our data also provide evidence that epigenetic mechanisms can contribute to the development of anxiety disorders.
Source: TSpace (University of Toronto)
Author: Dong Yao Wang
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2614970555