Feedback

miR-9 utilizes precursor pathways in adaptation to alcohol in mouse striatal neurons

Affiliation
Laboratory of Adaptation, Reward and Addiction ,Department of Animal Sciences ,Rutgers, The State University of New Jersey ,New Brunswick ,NJ ,United States
Mead, Edward Andrew;
Affiliation
Laboratory of Adaptation, Reward and Addiction ,Department of Animal Sciences ,Rutgers, The State University of New Jersey ,New Brunswick ,NJ ,United States
Wang, Yongping;
Affiliation
Thermo Fisher Scientific Inc. ,Austin ,TX ,United States
Patel, Sunali;
Affiliation
Laboratory of Adaptation, Reward and Addiction ,Department of Animal Sciences ,Rutgers, The State University of New Jersey ,New Brunswick ,NJ ,United States
Thekkumthala, Austin P.;
Affiliation
Laboratory of Adaptation, Reward and Addiction ,Department of Animal Sciences ,Rutgers, The State University of New Jersey ,New Brunswick ,NJ ,United States
Kepich, Rebecca;
Affiliation
Laboratory of Adaptation, Reward and Addiction ,Department of Animal Sciences ,Rutgers, The State University of New Jersey ,New Brunswick ,NJ ,United States
Benn-Hirsch, Elizabeth;
Affiliation
Laboratory of Adaptation, Reward and Addiction ,Department of Animal Sciences ,Rutgers, The State University of New Jersey ,New Brunswick ,NJ ,United States
Lee, Victoria;
Affiliation
Laboratory of Adaptation, Reward and Addiction ,Department of Animal Sciences ,Rutgers, The State University of New Jersey ,New Brunswick ,NJ ,United States
Basaly, Azra;
Affiliation
Department of Cell Biology and Biochemistry ,School of Medicine ,Texas Tech University Health Sciences Center ,Lubbock ,TX ,United States
Bergeson, Susan;
Affiliation
Department of Machine Learning ,Mohamed bin Zayed University of Artificial Intelligence ,Abu Dhabi ,United Arab Emirates
Siegelmann, Hava T.;
Affiliation
Laboratory of Adaptation, Reward and Addiction ,Department of Animal Sciences ,Rutgers, The State University of New Jersey ,New Brunswick ,NJ ,United States
Pietrzykowski, Andrzej Zbigniew

microRNA-9 (miR-9) is one of the most abundant microRNAs in the mammalian brain, essential for its development and normal function. In neurons, it regulates the expression of several key molecules, ranging from ion channels to enzymes, to transcription factors broadly affecting the expression of many genes. The neuronal effects of alcohol, one of the most abused drugs in the world, seem to be at least partially dependent on regulating the expression of miR-9. We previously observed that molecular mechanisms of the development of alcohol tolerance are miR-9 dependent. Since a critical feature of alcohol action is temporal exposure to the drug, we decided to better understand the time dependence of alcohol regulation of miR-9 biogenesis and expression. We measured the effect of intoxicating concentration of alcohol (20 mM ethanol) on the expression of all major elements of miR-9 biogenesis: three pri-precursors (pri-mir-9-1, pri-mir-9-2, pri-mir-9-3), three pre-precursors (pre-mir-9-1, pre-mir-9-2, pre-mir-9-3), and two mature microRNAs: miR-9-5p and miR-9-3p, using digital PCR and RT-qPCR, and murine primary medium spiny neurons (MSN) cultures. We subjected the neurons to alcohol based on an exposure/withdrawal matrix of different exposure times (from 15 min to 24 h) followed by different withdrawal times (from 0 h to 24 h). We observed that a short exposure increased mature miR-9-5p expression, which was followed by a gradual decrease and subsequent increase of the expression, returning to pre-exposure levels within 24 h. Temporal changes of miR-9-3p expression were complementing miR-9-5p changes. Interestingly, an extended, continuous presence of the drug caused a similar pattern. These results suggest the presence of the adaptive mechanisms of miR-9 expression in the presence and absence of alcohol. Measurement of miR-9 pre- and pri-precursors showed further that the primary effect of alcohol on miR-9 is through the mir-9-2 precursor pathway with a smaller contribution of mir-9-1 and mir-9-3 precursors. Our results provide new insight into the adaptive mechanisms of neurons to alcohol exposure. It would be of interest to determine next which microRNA-based mechanisms are involved in a transition from the acute, intoxicating effects of alcohol to the chronic, addictive effects of the drug.

Cite

Citation style:
Could not load citation form.

Access Statistic

Total:
Downloads:
Abtractviews:
Last 12 Month:
Downloads:
Abtractviews:

Rights

License Holder: Copyright © 2023 Mead, Wang, Patel, Thekkumthala, Kepich, Benn-Hirsch, Lee, Basaly, Bergeson, Siegelmann and Pietrzykowski.

Use and reproduction: