Effects of alcohol and PARP inhibition on RNA ribosomal engagement in cortical excitatory neurons.

Autor:	Krishnan HR; Center for Alcohol Research in Epigenetics, Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, United States., Vallerini GP; Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, United States., Gavin HE; Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, United States., Guizzetti M; Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, United States.; VA Portland Health Care System, Portland, OR, United States., Rizavi HS; Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, United States.; Jesse Brown Veterans Affairs Medical Center, Chicago, IL, United States., Gavin DP; Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, United States.; Jesse Brown Veterans Affairs Medical Center, Chicago, IL, United States., Sharma RP; Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, United States.; Jesse Brown Veterans Affairs Medical Center, Chicago, IL, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in molecular neuroscience [Front Mol Neurosci] 2023 Apr 11; Vol. 16, pp. 1125160. Date of Electronic Publication: 2023 Apr 11 (Print Publication: 2023).
DOI:	10.3389/fnmol.2023.1125160
Abstrakt:	We report on the effects of ethanol (EtOH) and Poly (ADP-ribose) polymerase (PARP) inhibition on RNA ribosomal engagement, as a proxy for protein translation, in prefrontal cortical (PFC) pyramidal neurons. We hypothesized that EtOH induces a shift in RNA ribosomal-engagement (RE) in PFC pyramidal neurons, and that many of these changes can be reversed using a PARP inhibitor. We utilized the translating ribosome affinity purification (TRAP) technique to isolate cell type-specific RNA. Transgenic mice with EGFP-tagged Rpl10a ribosomal protein expressed only in CaMKIIα-expressing pyramidal cells were administered EtOH or normal saline (CTL) i.p. twice a day, for four consecutive days. On the fourth day, a sub-group of mice that received EtOH in the previous three days received a combination of EtOH and the PARP inhibitor ABT-888 (EtOH + ABT-888). PFC tissue was processed to isolate both, CaMKIIα pyramidal cell-type specific ribosomal-engaged RNA (TRAP-RNA), as well as genomically expressed total-RNA from whole tissue, which were submitted for RNA-seq. We observed EtOH effects on RE transcripts in pyramidal cells and furthermore treatment with a PARP inhibitor "reversed" these effects. The PARP inhibitor ABT-888 reversed 82% of the EtOH-induced changes in RE (TRAP-RNA), and similarly 83% in the total-RNA transcripts. We identified Insulin Receptor Signaling as highly enriched in the ethanol-regulated and PARP-reverted RE pool and validated five participating genes from this pathway. To our knowledge, this is the first description of the effects of EtOH on excitatory neuron RE transcripts from total-RNA and provides insights into PARP-mediated regulation of EtOH effects. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Krishnan, Vallerini, Gavin, Guizzetti, Rizavi, Gavin and Sharma.)
Databáze:	MEDLINE
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