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ORIGINAL RESEARCH article

Front. Cell. Neurosci.
Sec. Cellular Neurophysiology
Volume 18 - 2024 | doi: 10.3389/fncel.2024.1474992

Early life stress induces decreased expression of CB1R and FAAH and epigenetic changes in the medial prefrontal cortex of male rats

Provisionally accepted
Arijana Demaili Arijana Demaili 1Ana Portugalov Ana Portugalov 2,3Mouna Maroun Mouna Maroun 3,4Irit Akirav Irit Akirav 2,3Anna K. Braun Anna K. Braun 1,5Joerg Bock Joerg Bock 5,6*
  • 1 Institute of Biology, Department of Zoology/Developmental Neurobiology, Otto von Guericke University Magdeburg, Magdeburg, Germany
  • 2 Department of Psychology, School of Psychology, University of Haifa, Hiafa, Israel
  • 3 Integrated Brain and Behavior Research Center, University of Haifa, Haifa, Haifa, Israel
  • 4 Sagol Department of Neurobiology, Faculty of Natural Sciences, University of Haifa, Mount Carmel, Haifa, Israel
  • 5 Center for Behavioral Brain Sciences, Magdeburg, Saxony-Anhalt, Germany
  • 6 Institute of Biology, PG Epigenetics and Structural Plasticity, Otto von Guericke University Magdeburg, Magdeburg, Germany

The final, formatted version of the article will be published soon.

    Several studies in both animal models and in humans have provided substantial evidence that early life stress (ELS) induces long-term changes in behavior and brain function, making it a significant risk factor in the aetiology of various mental disorders, including anxiety and depression. In this study, we tested the hypothesis that ELS in male rats (i) leads to increased anxiety and depressivelike symptoms; and (ii) that these behavioral changes are associated with functional alterations in the endocannabinoid system of the medial prefrontal cortex (mPFC). We further assessed whether the predicted changes in the gene expression of two key components of the endocannabinoid system, cannabinoid receptor 1 (CB1R) and the fatty acid amide hydrolase (FAAH), are regulated by epigenetic mechanisms. Behavioral profiling revealed that the proportion of behaviorally affected animals was increased in ELS exposed male rats compared to control animals, specifically showing symptoms of anhedonia and impaired social behavior. On the molecular level we observed a decrease in CB1R and FAAH mRNA expression in the mPFC of adult ELS exposed animals. These gene expression changes were accompanied by reduced global histone 3 acetylation in the mPFC, while no significant changes in DNA methylation and no significant changes of histone-acetylation at the promoter regions of the analyzed genes were detected. Taken together, our data provide evidence that ELS induces a long-term reduction of CB1R and FAAH expression in the mPFC of adult male rats, which may partially contribute to the ELS-induced changes in adult socio-emotional behavior.

    Keywords: early life stress, Pefrontal cortex, endocannabinoid system, endocannabinoid receptor 1, epigenetics

    Received: 02 Aug 2024; Accepted: 07 Oct 2024.

    Copyright: © 2024 Demaili, Portugalov, Maroun, Akirav, Braun and Bock. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Joerg Bock, Institute of Biology, PG Epigenetics and Structural Plasticity, Otto von Guericke University Magdeburg, Magdeburg, 39120, Germany

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