Open Accessmi RNA ‐regulated transcription associated with mouse strains predisposed to hypnotic effects of ethanol
Author(s) -
Vestal B.,
Russell P.,
Radcliffe R.A.,
Bemis L.,
Saba L.M.,
Kechris K.
Publication year - 2018
Publication title -
brain and behavior
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.915
H-Index - 41
ISSN - 2162-3279
DOI - 10.1002/brb3.989
Subject(s) - rna , messenger rna , biology , gabaa receptor , receptor , microbiology and biotechnology , microrna , small rna , pharmacology , biochemistry , gene
Studying innate sensitivity to ethanol can be an important first step toward understanding alcohol use disorders. In brain, we investigated transcripts, with evidence of mi RNA modulation related to a predisposition to the hypnotic effect of ethanol, as measured by loss of righting reflex ( LORR ). Methods Expression of mi RNA s (12 samples) and expression of mRNA s (353 samples) in brain were independently analyzed for an association with LORR in mice from the LXS recombinant inbred panel gathered across several small studies. These results were then integrated via a meta‐analysis of mi RNA – mRNA target pairs identified in mi RNA ‐target interaction databases. Results We found 112 significant mi RNA – mRNA pairs where a large majority of mi RNA s and mRNA s were highly interconnected. Most pairs indicated a pattern of increased levels of mi RNA s and reduced levels of mRNA s being associated with more alcohol‐sensitive strains. For example, CaMKIIn1 was targeted by multiple miRNAs associated with LORR. CAMK2N1 is an inhibitor of CAMK 2, which among other functions, phosphorylates, or binds to GABA A and NMDA receptors. Conclusions Our results suggest a novel role of mi RNA ‐mediated regulation of an inhibitor of CAMK 2 and its downstream targets including the GABA A and NMDA receptors, which have been previously implicated to have a role in ethanol‐induced sedation and sensitivity.