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ORIGINAL RESEARCH article

Front. Psychiatry
Sec. Anxiety and Stress Disorders
Volume 15 - 2024 | doi: 10.3389/fpsyt.2024.1472194

Single prolonged stress induces behavior and transcriptomic changes in the medial prefrontal cortex to increase susceptibility to anxiety-like behavior in rats

Provisionally accepted
Javed Iqbal Javed Iqbal 1Geng-Di Huang Geng-Di Huang 1Dan Shen Dan Shen 2Yan-Xue Xue Yan-Xue Xue 3Mei Yang Mei Yang 1Xiaojian Jia Xiaojian Jia 1*
  • 1 Department of Addiction Medicine, Shenzhen KangNing Hospital, Shenzhen, China
  • 2 Xinxiang Medical University, Xinxiang, Henan Province, China
  • 3 Peking University, Beijing, Beijing Municipality, China

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

    Transcriptomic studies offer valuable insights into the pathophysiology of traumatic stressinduced neuropsychiatric disorders, including generalized anxiety disorder and post-traumatic stress disorder (PTSD). The medial prefrontal cortex (mPFC) has been implicated in emotion, cognitive function, and psychiatric disorders. Alterations in the function of mPFC have been observed in PTSD patients. However, the specific transcriptomic mechanisms governed by genes within the mPFC under traumatic stress remain elusive. In this study, we addressed this knowledge gap by conducting transcriptome-wide RNA-seq analysis in the prelimbic (PL) and infralimbic (IL) cortices. We employed the single prolonged stress (SPS) animal model to simulate anxiety-like behavior, which was assessed using the open field and elevated plus maze tests. We identified sixty-two differentially expressed genes (DEGs) (FDR adjusted p < 0.05) with significant expression changes in the PL and IL mPFC. In the PL cortex, DEGs in the susceptible group exhibited reduced enrichment for cellular, biological, and molecular functions such as postsynaptic density proteins, glutamatergic synapses, synapse formation, transmembrane transport proteins, and actin cytoskeleton reorganization. In contrast, the ILsusceptible group displayed diminished enrichment for synapse formation, neuronal activity, dendrite development, axon regeneration, learning processes, and glucocorticoid receptor binding compared to control and insusceptible groups. DEGs in the PL-susceptible group were enriched for Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related to Parkinson's disease, Huntington's disease, Alzheimer's disease, and neurodegeneration processes. In the IL cortex, the susceptible group demonstrated enrichment for KEGG pathways involved in regulating stress signaling pathways and addiction-like behaviors, compared to control and insusceptible groups. The enhanced enrichment of these KEGG pathways in the PL and IL mPFC may underlie the anxiety-like behavior observed in susceptible rats.

    Keywords: traumatic stress, Prefrontal Cortex, susceptibility, resilient, Anxiety

    Received: 29 Jul 2024; Accepted: 28 Oct 2024.

    Copyright: © 2024 Iqbal, Huang, Shen, Xue, Yang and Jia. 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: Xiaojian Jia, Department of Addiction Medicine, Shenzhen KangNing Hospital, Shenzhen, China

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