Conclusion
A novel role for GABA is demonstrated in which it acts as an HDAC inhibitor. The present study expands the horizons for exploring the non-neurotransmitter functions of GABA.
Results
It is found that GABA inhibits HDAC1/2/3 expression and upregulates histone acetylation levels (Ace-H3K9/Ace-H4K12) in SH-SY5Y cells (which express GABA receptors), 3T3-L1 cells (which do not express GABA receptors), and the cerebral cortex in mice. Glutamate receptor 2 (GluR2) is a subunit of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor and is implicated in the pathogenesis of some neurological diseases. It is also found that GABA increases GluR2 expression by inhibiting HDAC1/2 but not HDAC3.