| Title: | Plasticity of gene expression in the nervous system by exposure to environmental odorants that inhibit HDACs |
| Author(s): | Haga-Yamanaka S; Nunez-Flores R; Scott CA; Perry S; Chen ST; Pontrello C; Nair MG; Ray A; |
| DOI: | 10.1101/2023.02.21.529339 |
| Abstract: | "Eukaryotes are often exposed to microbes and respond to their secreted metabolites, such as the microbiome in animals or commensal bacteria in roots. Little is known about the effects of long-term exposure to volatile chemicals emitted by microbes, or other volatiles that we are exposed to over a long duration. Using the model system Drosophila melanogaster we evaluate a yeast emitted volatile, diacetyl, found in high levels around fermenting fruits where they spend long periods of time. We find that exposure to just the headspace containing the volatile molecules can alter gene expression in the antenna. Experiments showed that diacetyl and structurally related volatile compounds inhibited human histone-deacetylases (HDACs), increased histone-H3K9 acetylation in human cells, and caused wide changes in gene expression in both Drosophila and mice. Diacetyl crosses the blood-brain barrier and exposure causes modulation of gene expression in the brain, therefore has potential as a therapeutic. Using two separate disease models known to be responsive to HDAC-inhibitors, we evaluated physiological effects of volatile exposure. First, we find that the HDAC inhibitor also halts proliferation of a neuroblastoma cell line in culture as predicted. Next, exposure to vapors slows progression of neurodegeneration in a Drosophila model for Huntington's disease. These changes strongly suggest that unbeknown to us, certain volatiles in the surroundings can have profound effects on histone acetylation, gene expression and physiology in animals. SIGNIFICANCE STATEMENT: Volatile compounds are ubiquitous and are produced by most organisms. We report that some volatile compounds emitted from microbes and present in food, can alter epigenetic states in neurons and other eukaryotic cells. These volatile organic compounds act as inhibitors of HDACs and over time periods of hours and days cause dramatic modulation of gene expression even from a physically separated emission source. Given their HDAC-inhibitory properties the VOCs also act as therapeutics in preventing proliferation of neuroblastoma cells and degeneration of neurons in a Huntington's disease model" |
| Notes: | "PubMed-not-MEDLINEHaga-Yamanaka, Sachiko Nunez-Flores, Rogelio Scott, Christi Ann Perry, Sarah Chen, Stephanie Turner Pontrello, Crystal Nair, Meera Goh Ray, Anandasankar eng Preprint 2023/03/04 bioRxiv. 2023 Feb 21:2023.02.21.529339. doi: 10.1101/2023.02.21.529339. Preprint" |
