The lncRNA BDNF-AS is an epigenetic regulator in the human amygdala in early onset alcohol use disorders
| Autor: | Svetlana Dzitoyeva, Subhash C. Pandey, Evan J. Kyzar, Tara Teppen, John Peyton Bohnsack |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Behavioral epigenetics Late onset Amygdala Article lcsh:RC321-571 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Downregulation and upregulation Neurotrophic factors Internal medicine medicine Humans Enhancer of Zeste Homolog 2 Protein Epigenetics lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Biological Psychiatry Arc (protein) Neuronal Plasticity business.industry Brain-Derived Neurotrophic Factor Middle Aged Psychiatry and Mental health Alcoholism Cytoskeletal Proteins 030104 developmental biology Endocrinology medicine.anatomical_structure nervous system Case-Control Studies Synaptic plasticity Female RNA Long Noncoding business 030217 neurology & neurosurgery |
| Zdroj: | Translational Psychiatry, Vol 9, Iss 1, Pp 1-11 (2019) Translational Psychiatry |
| ISSN: | 2158-3188 |
| DOI: | 10.1038/s41398-019-0367-z |
| Popis: | Adolescent alcohol drinking is known to contribute to the development and severity of alcohol use disorders (AUDs) later in adulthood. Recent studies have shown that long non-coding RNAs (lncRNAs) are critical for brain development and synaptic plasticity. One such lncRNA is natural occurring brain-derived neurotrophic factor antisense (BDNF-AS) that has been shown to regulate BDNF expression. The role of BDNF-AS lncRNA in the molecular mechanisms of AUD is unknown. Here, we evaluated the expression and functional role of BDNF-AS in postmortem amygdala of either early onset or late onset alcoholics (individuals who began drinking before or after 21 years of age, respectively) and age-matched control subjects. BDNF-AS expression is increased in early onset but not in late onset AUD amygdala and appears to be regulated epitranscriptomically via decreased N6-methyladenosine on BDNF-AS. Upregulation of BDNF-AS is associated with a significant decrease in BDNF expression and increased recruitment of EZH2, which deposits repressive H3K27 trimethylation (H3K27me3) at regulatory regions in the BDNF gene in the early onset AUD group. Drinking during adolescence also contributed to significant decreases in activity-regulated cytoskeleton-associated protein (ARC) expression which also appeared to be mediated by increased EZH2 deposition of repressive H3K27me3 at the ARC synaptic activity response element. These results suggest an important role for BDNF-AS in the regulation of synaptic plasticity via epigenetic reprogramming in the amygdala of AUD subjects who began drinking during adolescence. |
| Databáze: | OpenAIRE |
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