Transcriptomics

Dataset Information

0

Methamphetamine administration causes differential alterations in gene expression and dynamic patterns of histone acetylation/hypoacetylation in the rat nucleus accumbens


ABSTRACT: Methamphetamine (METH) addiction is associated with a plethora of neuropsychiatric symptoms. In rodents, administration of the drug is accompanied by complex changes in gene expression in the dorsal striatum. Very little is known about the effects of the drug on gene expression and epigenetic modifications in the nucleus accumbens (NAc). The present study was conducted in order to investigate the effects of a single injection of METH on gene expression in that structure. We also queried whether changes in transcript levels were accompanied by alterations in histone acetylation as well as in the expression of the histone acetyltransferase (HAT), ATF2, and of the histone deacetylases (HDACs), HDAC1 and HDAC2. Microarray analyses revealed that METH caused significant time-dependent increases in the expression of several genes that had previously been implicated in the acute and longterm effects of psychostimulants in the brain. These include several immediate early genes (c-fos, Egrs, c-jun, and Nurr1) and corticotropin-releasing factor (Crf). There were also increases in the levels of neuromedin U, Tnf-alpha, and Kcnk18, among others. In contrast, the METH injection caused decreases in the expression of many genes including Npas4 and cholecystokin (Cck). Pathway analyses showed that differentially affected genes participate in behavioral performance, cell-to-cell signaling and interactions, and regulation of gene expression. Other differentially affected genes are known to be involved in cellular compromise and death pathways. PCR analyses were used to confirm the changes in the expression of c-fos, fosB, c-jun, junB, Crf, NmU, Cck, and Npas4 transcripts. Western blot analyses also identified METH-mediated decreases in the acetylation of histone H3 at lysine 9 (H3K9) and lysine 18 (H3K18) as well as in histone 4 at lysine 16 (H4K16). In contrast, the METH injection caused time-dependent increases in the acetylation of H4K8 and H4K12. The changes in histone acetylation were also accompanied by decreased expression of HDAC1 but increased expression of ATF2 and of HDAC2. These results suggest that METH-induced alterations in global gene expression might be due, in part, to diverse effects of METH-induced histone acetylation secondary to changes in HAT and HDAC expression.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE31081 | GEO | 2011/08/01

SECONDARY ACCESSION(S): PRJNA144731

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2011-07-31 | E-GEOD-31081 | biostudies-arrayexpress
2013-06-30 | GSE46717 | GEO
2013-06-30 | E-GEOD-46717 | biostudies-arrayexpress
2021-02-04 | GSE166095 | GEO
2021-02-04 | GSE166094 | GEO
2013-02-28 | E-GEOD-42776 | biostudies-arrayexpress
2013-02-28 | GSE42776 | GEO
2014-03-30 | E-MTAB-2184 | biostudies-arrayexpress
2010-09-21 | GSE24233 | GEO
2010-09-21 | E-GEOD-24233 | biostudies-arrayexpress