Functional involvement of septal miR-132 in extinction and oxytocin-mediated reversal of social fear
Uloženo v:
| Název: | Functional involvement of septal miR-132 in extinction and oxytocin-mediated reversal of social fear |
|---|---|
| Autoři: | Anna Bludau, Uwe Schwartz, Daniela M. Zeitler, Melanie Royer, Gunter Meister, Inga D. Neumann, Rohit Menon |
| Zdroj: | Mol Psychiatry |
| Informace o vydavateli: | Springer Science and Business Media LLC, 2023. |
| Rok vydání: | 2023 |
| Témata: | Male, Neurons, Conditioning, Classical, 38/77, Mice, Inbred C57BL [MeSH], Receptors, Oxytocin/genetics [MeSH], 42/41, 38/90, 631/337, Septum of Brain/metabolism [MeSH], Receptors, Oxytocin/metabolism [MeSH], 38/39, 38/61, Male [MeSH], Conditioning, Classical/physiology [MeSH], Extinction, Psychological/physiology [MeSH], MicroRNAs/genetics [MeSH], MicroRNAs/metabolism [MeSH], Neurons/metabolism [MeSH], Extinction, Psychological/drug effects [MeSH], Animals [MeSH], 64/60, Social Behavior [MeSH], Mice [MeSH], Article, Oxytocin/metabolism [MeSH], Fear/physiology [MeSH], Septum of Brain/drug effects [MeSH], 631/378, article, Fear, Oxytocin, 590 Tiere (Zoologie), Extinction, Psychological, Mice, Inbred C57BL, MicroRNAs, Mice, Receptors, Oxytocin, Molecular biology, Neuroscience, ddc:590, Animals, 570 Biowissenschaften, Biologie, Septum of Brain, ddc:570, 500 Naturwissenschaften, Social Behavior |
| Popis: | Social interactions are critical for mammalian survival and evolution. Dysregulation of social behavior often leads to psychopathologies such as social anxiety disorder, denoted by intense fear and avoidance of social situations. Using the social fear conditioning (SFC) paradigm, we analyzed expression levels of miR-132-3p and miR-124-3p within the septum, a brain region essential for social preference and avoidance behavior, after acquisition and extinction of social fear. Here, we found that SFC dynamically altered both microRNAs. Functional in vivo approaches using pharmacological strategies, inhibition of miR-132-3p, viral overexpression of miR-132-3p, and shRNA-mediated knockdown of miR-132-3p specifically within oxytocin receptor-positive neurons confirmed septal miR-132-3p to be critically involved not only in social fear extinction, but also in oxytocin-induced reversal of social fear. Moreover, Argonaute-RNA-co-immunoprecipitation-microarray analysis and further in vitro and in vivo quantification of target mRNA and protein, revealed growth differentiation factor-5 (Gdf-5) as a target of miR-132-3p. Septal application of GDF-5 impaired social fear extinction suggesting its functional involvement in the reversal of social fear. In summary, we show that septal miR-132-3p and its downstream target Gdf-5 regulate social fear expression and potentially mediate oxytocin-induced reversal of social fear. |
| Druh dokumentu: | Article Other literature type |
| Popis souboru: | application/pdf |
| Jazyk: | English |
| ISSN: | 1476-5578 1359-4184 |
| DOI: | 10.1038/s41380-023-02309-3 |
| DOI: | 10.5283/epub.55023 |
| DOI: | 10.1038/s41380-023-02309-310.5283/epub.55023 |
| Přístupová URL adresa: | https://pubmed.ncbi.nlm.nih.gov/37938765 https://repository.publisso.de/resource/frl:6500691 https://epub.uni-regensburg.de/55023/ |
| Rights: | CC BY URL: http://creativecommons.org/licenses/by/4.0/ Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (http://creativecommons.org/licenses/by/4.0/) . |
| Přístupové číslo: | edsair.doi.dedup.....9aec62bc075b684e20a495bc8e04f985 |
| Databáze: | OpenAIRE |
Full Text Finder 
Nájsť tento článok vo Web of Science | Abstrakt: | Social interactions are critical for mammalian survival and evolution. Dysregulation of social behavior often leads to psychopathologies such as social anxiety disorder, denoted by intense fear and avoidance of social situations. Using the social fear conditioning (SFC) paradigm, we analyzed expression levels of miR-132-3p and miR-124-3p within the septum, a brain region essential for social preference and avoidance behavior, after acquisition and extinction of social fear. Here, we found that SFC dynamically altered both microRNAs. Functional in vivo approaches using pharmacological strategies, inhibition of miR-132-3p, viral overexpression of miR-132-3p, and shRNA-mediated knockdown of miR-132-3p specifically within oxytocin receptor-positive neurons confirmed septal miR-132-3p to be critically involved not only in social fear extinction, but also in oxytocin-induced reversal of social fear. Moreover, Argonaute-RNA-co-immunoprecipitation-microarray analysis and further in vitro and in vivo quantification of target mRNA and protein, revealed growth differentiation factor-5 (Gdf-5) as a target of miR-132-3p. Septal application of GDF-5 impaired social fear extinction suggesting its functional involvement in the reversal of social fear. In summary, we show that septal miR-132-3p and its downstream target Gdf-5 regulate social fear expression and potentially mediate oxytocin-induced reversal of social fear. |
|---|---|
| ISSN: | 14765578 13594184 |
| DOI: | 10.1038/s41380-023-02309-3 |