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Cited by 22Memory and Neural MechanismsMicroRNA in disease regulationNeuroscience and Neuropharmacology Research

A role for miR-132 in learned safety

Open access
Ronovsky, Marianne, Zambon, Alice, Cicvaric, Ana, Boehm, Vincent, Hoesel, Bastian, Moser, Bernhard A., Yang, Jiaye, Schmid, Johannes A. +3 more·2019·Scientific Reports
DOI 10.1038/s41598-018-37054-zPMC PMC6346013
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Abstract

Learned safety is a fear inhibitory mechanism, which regulates fear responses, promotes episodes of safety and generates positive affective states. Despite its potential as experimental model for several psychiatric illnesses, including post-traumatic stress disorder and depression, the molecular mechanisms of learned safety remain poorly understood, We here investigated the molecular mediators of learned safety, focusing on the characterization of miRNA expression in the basolateral amygdala (BLA). Comparing levels of 22 miRNAs in learned safety and learned fear trained mice, six safety-related miRNAs, including three members of the miR-132/-212 family, were identified. A gain-of-function approach based upon in-vivo transfection of a specific miRNA mimic, and miR-132/212 knock-out mice as loss-of-function tool were used in order to determine the relevance of miR-132 for learned safety at the behavioral and the neuronal functional levels. Using a designated bioinformatic approach, PTEN and GAT1 were identified as potential novel miR-132 target genes and further experimentally validated. We here firstly provide evidence for a regulation of amygdala miRNA expression in learned safety and propose miR-132 as signature molecule to be considered in future preclinical and translational approaches testing the transdiagnostic relevance of learned safety as intermediate phenotype in fear and stress-related disorders.

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  • miR-26a-3p and miR-132 can induce depressive symptoms by activating the PTEN/PI3K/Akt signaling pathway.

    “miR-26a-3p263 and miR-132264 can induce depressive symptoms by activating the phosphatase and tensin homolog (PTEN)/phosphoinositide 3-kinase (PI3K)/Akt signaling pathway”

    From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [264]

    The Results (miR-132 target gene analysis; page unavailable) show that increasing miR-132 reduced PTEN expression in cultured cells. The Discussion (page unavailable) proposes a role for miR-132 and PTEN in learned safety, but the paper does not show that miR-132 induces depressive symptoms through activation of a PTEN/PI3K/Akt pathway. The adjacent miR-26a-3p citation is not attributed to this source. (LLM, conf=0.87)

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Cited by

Sorted by citations

Authors
Ronovsky, M., Zambon, A., Cicvaric, A., Boehm, V., Hoesel, B., Moser, B. A., Yang, J., Schmid, J. A., Haubensak, W. E., Monje, F. J., & Pollak, D. D.
Affiliations
  • Medical University of Vienna (AT)
  • Research Institute of Molecular Pathology (AT)
Corresponding author
Pollak, Daniela D.
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2019-01-24
Volume
9
Issue
1
Pages
528-528
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-018-37054-z
PMC
PMC6346013
OpenAlex
W2924088715
Cited by
22
References
8
Citations by year
2026: 1 · 2024: 1 · 2023: 7 · 2022: 2 · 2021: 5 · 2020: 3 · 2019: 3
FWCI
1.89
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • EC | European Research Council (311701)
  • Austrian Science Fund (P 31004)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
miR-132, microRNA expression, basolateral amygdala, fear inhibition, fear extinction, PTEN, GABA transporter 1, post-traumatic stress disorder, depression, stress-related disorders
MeSH terms
Animals, Conditioning, Psychological, Fear, Gene Expression Regulation, Male, Mice, Inbred C57BL, 3T3 Cells, MicroRNAs, Mice, Basolateral Nuclear Complex

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