Methamphetamine induced regional-specific transcriptomic and epigenetic changes in rat brain [ATAC-seq]

ABSTRACT: We investigated the transcriptomic and epigenetic responses to a METH overdose in four regions of rat brain, including the nucleus accumbens, dentate gyrus, Ammon’s horn, and subventricular zone. We found that 24 hours after the METH overdose, 15.6% of genes changed expression and 27.6% of open-chromatin regions altered chromatin accessibility in all four rat brain regions. Interestingly, only a few of those differentially expressed genes (DEGs) and differentially accessible regions (DARs) were simultaneously affected. Among the four rat brain regions analyzed, 149 transcription factors (TFs) and 31 epigenetic factors were significantly affected by the METH overdose. The METH overdose also resulted in reversed regulation patterns of both gene and chromatin accessibility in the dentate gyrus and Ammon’s horn. About 70% of METH-induced chromatin accessibility alterations are highly enriched in neurological processes and shared conserved sequences to the human genome. Many of these conserved regions were active brain-specific enhancers and harbored the SNPs associated with human neurological functions and diseases. Our results indicate strong region-specific transcriptomic and epigenetic responses to a METH overdose in distinct rat brain regions. We describe the conservation of region-specific gene regulatory networks associated with a METH overdose. Overall, our study provides clues to a better understanding of the molecular responses to METH overdose in the human brain.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE199260 | GEO | 2023/07/20

REPOSITORIES: GEO