MicroRNA-mediated translational pathways are regulated in the orbitofrontal cortex and peripheral blood samples during acute abstinence from heroin self-administration
Opioid misuse in the United States contributes to >70% of annual overdose deaths. To develop additional therapeutics that may prevent opioid misuse, further studies on the neurobiological consequences of opioid exposure are needed. Here we sought to characterize molecular neuroadaptations inv...
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| Format: | Article |
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Frontiers Media S.A.
2023-08-01
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| Series: | Advances in Drug and Alcohol Research |
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| Online Access: | https://www.frontierspartnerships.org/articles/10.3389/adar.2023.11668/full |
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| author | Mary Tresa Zanda Mary Tresa Zanda Leila Saikali Leila Saikali Paige Morris Paige Morris Stephanie E. Sillivan Stephanie E. Sillivan |
| author_facet | Mary Tresa Zanda Mary Tresa Zanda Leila Saikali Leila Saikali Paige Morris Paige Morris Stephanie E. Sillivan Stephanie E. Sillivan |
| author_sort | Mary Tresa Zanda |
| collection | DOAJ |
| description | Opioid misuse in the United States contributes to >70% of annual overdose deaths. To develop additional therapeutics that may prevent opioid misuse, further studies on the neurobiological consequences of opioid exposure are needed. Here we sought to characterize molecular neuroadaptations involving microRNA (miRNA) pathways in the brain and blood of adult male rats that self-administered the opioid heroin. miRNAs are ∼18–24 nucleotide RNAs that regulate protein expression by preventing mRNA translation into proteins. Manipulation of miRNAs and their downstream pathways can critically regulate drug seeking behavior. We performed small-RNA sequencing of miRNAs and proteomics profiling on tissue from the orbitofrontal cortex (OFC), a brain region associated with heroin seeking, following 2 days of forced abstinence from self-administration of 0.03 mg/kg/infusion heroin or sucrose. Heroin self-administration resulted in a robust shift of the OFC miRNA profile, regulating 77 miRNAs, while sucrose self-administration only regulated 9 miRNAs that did not overlap with the heroin-induced profile. Conversely, proteomics revealed dual regulation of seven proteins by both heroin and sucrose in the OFC. Pathway analysis determined that heroin-associated miRNA pathways are predicted to target genes associated with the term “prion disease,” a term that was also enriched in the heroin-induced protein expression dataset. Lastly, we confirmed that a subset of heroin-induced miRNA expression changes in the OFC are regulated in peripheral serum and correlate with heroin infusions. These findings demonstrate that peripheral blood samples may have biomarker utility for assessment of drug-induced miRNA pathway alterations that occur in the brain following chronic drug exposure. |
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| format | Article |
| id | doaj.art-d100f9ba4d204a26a0d491be1891d1a6 |
| institution | Directory Open Access Journal |
| issn | 2674-0001 |
| language | English |
| last_indexed | 2024-03-12T15:01:53Z |
| publishDate | 2023-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Advances in Drug and Alcohol Research |
| spelling | doaj.art-d100f9ba4d204a26a0d491be1891d1a62023-08-14T04:11:17ZengFrontiers Media S.A.Advances in Drug and Alcohol Research2674-00012023-08-01310.3389/adar.2023.1166811668MicroRNA-mediated translational pathways are regulated in the orbitofrontal cortex and peripheral blood samples during acute abstinence from heroin self-administrationMary Tresa Zanda0Mary Tresa Zanda1Leila Saikali2Leila Saikali3Paige Morris4Paige Morris5Stephanie E. Sillivan6Stephanie E. Sillivan7Center for Substance Abuse Research, Temple University, Philadelphia, PA, United StatesDepartment of Neural Sciences, Temple University, Philadelphia, PA, United StatesCenter for Substance Abuse Research, Temple University, Philadelphia, PA, United StatesCollege of Liberal Arts, Temple University, Philadelphia, PA, United StatesCenter for Substance Abuse Research, Temple University, Philadelphia, PA, United StatesDepartment of Neural Sciences, Temple University, Philadelphia, PA, United StatesCenter for Substance Abuse Research, Temple University, Philadelphia, PA, United StatesDepartment of Neural Sciences, Temple University, Philadelphia, PA, United StatesOpioid misuse in the United States contributes to >70% of annual overdose deaths. To develop additional therapeutics that may prevent opioid misuse, further studies on the neurobiological consequences of opioid exposure are needed. Here we sought to characterize molecular neuroadaptations involving microRNA (miRNA) pathways in the brain and blood of adult male rats that self-administered the opioid heroin. miRNAs are ∼18–24 nucleotide RNAs that regulate protein expression by preventing mRNA translation into proteins. Manipulation of miRNAs and their downstream pathways can critically regulate drug seeking behavior. We performed small-RNA sequencing of miRNAs and proteomics profiling on tissue from the orbitofrontal cortex (OFC), a brain region associated with heroin seeking, following 2 days of forced abstinence from self-administration of 0.03 mg/kg/infusion heroin or sucrose. Heroin self-administration resulted in a robust shift of the OFC miRNA profile, regulating 77 miRNAs, while sucrose self-administration only regulated 9 miRNAs that did not overlap with the heroin-induced profile. Conversely, proteomics revealed dual regulation of seven proteins by both heroin and sucrose in the OFC. Pathway analysis determined that heroin-associated miRNA pathways are predicted to target genes associated with the term “prion disease,” a term that was also enriched in the heroin-induced protein expression dataset. Lastly, we confirmed that a subset of heroin-induced miRNA expression changes in the OFC are regulated in peripheral serum and correlate with heroin infusions. These findings demonstrate that peripheral blood samples may have biomarker utility for assessment of drug-induced miRNA pathway alterations that occur in the brain following chronic drug exposure.https://www.frontierspartnerships.org/articles/10.3389/adar.2023.11668/fullmicroRNAheroinopioidbiomarkerself-administration |
| spellingShingle | Mary Tresa Zanda Mary Tresa Zanda Leila Saikali Leila Saikali Paige Morris Paige Morris Stephanie E. Sillivan Stephanie E. Sillivan MicroRNA-mediated translational pathways are regulated in the orbitofrontal cortex and peripheral blood samples during acute abstinence from heroin self-administration Advances in Drug and Alcohol Research microRNA heroin opioid biomarker self-administration |
| title | MicroRNA-mediated translational pathways are regulated in the orbitofrontal cortex and peripheral blood samples during acute abstinence from heroin self-administration |
| title_full | MicroRNA-mediated translational pathways are regulated in the orbitofrontal cortex and peripheral blood samples during acute abstinence from heroin self-administration |
| title_fullStr | MicroRNA-mediated translational pathways are regulated in the orbitofrontal cortex and peripheral blood samples during acute abstinence from heroin self-administration |
| title_full_unstemmed | MicroRNA-mediated translational pathways are regulated in the orbitofrontal cortex and peripheral blood samples during acute abstinence from heroin self-administration |
| title_short | MicroRNA-mediated translational pathways are regulated in the orbitofrontal cortex and peripheral blood samples during acute abstinence from heroin self-administration |
| title_sort | microrna mediated translational pathways are regulated in the orbitofrontal cortex and peripheral blood samples during acute abstinence from heroin self administration |
| topic | microRNA heroin opioid biomarker self-administration |
| url | https://www.frontierspartnerships.org/articles/10.3389/adar.2023.11668/full |
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