The Role of Microglia in the (Mal)adaptive Response to Traumatic Experience in an Animal Model of PTSD

Kesem Nahum, Doron Todder, Joseph Zohar, Hagit Cohen

    Research output: Contribution to journalArticlepeer-review

    9 Scopus citations

    Abstract

    The present study investigates whether predator scent-stress (PSS) shifts the microglia from a quiescent to a chronically activated state and whether morphological alterations in microglial activation differ between individuals displaying resilient vs. vulnerable phenotypes. In addition, we examined the role that GC receptors play during PSS exposure in the impairment of microglial activation and thus in behavioral response. Adult male Sprague Dawley rats were exposed to PSS or sham-PSS for 15 min. Behaviors were assessed with the elevated plus-maze (EPM) and acoustic startle response (ASR) paradigms 7 days later. Localized brain expression of Iba-1 was assessed, visualized, and classified based on their morphology and stereological counted. Hydrocortisone and RU486 were administered systemically 10 min post PSS exposure and behavioral responses were measured on day 7 and hippocampal expression of Ionized calcium-binding adaptor molecule 1 (Iba-1) was subsequently evaluated. Animals whose behavior was extremely disrupted (PTSD-phenotype) selectively displayed excessive expression of Iba-1 with concomitant downregulation in the expression of CX3C chemokine receptor 1 (CX3CR1) in hippocampal structures as compared with rats whose behavior was minimally or partially disrupted. Changes in microglial morphology have also been related only to the PTSD-phenotype group. These data indicate that PSS-induced microglia activation in the hippocampus serves as a critical mechanistic link between the HPA-axis and PSS-induced impairment in behavioral responses.

    Original languageEnglish
    Article number7185
    JournalInternational Journal of Molecular Sciences
    Volume23
    Issue number13
    DOIs
    StatePublished - 1 Jul 2022

    Keywords

    • animal models
    • chemokine
    • immune system
    • microglia
    • post-traumatic stress disorder (PTSD)

    ASJC Scopus subject areas

    • Molecular Biology
    • Spectroscopy
    • Catalysis
    • Inorganic Chemistry
    • Computer Science Applications
    • Physical and Theoretical Chemistry
    • Organic Chemistry

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