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


Journal

International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791

Informations de publication

Date de publication:
28 Jun 2022
Historique:
received: 12 05 2022
revised: 22 06 2022
accepted: 23 06 2022
entrez: 9 7 2022
pubmed: 10 7 2022
medline: 14 7 2022
Statut: epublish

Résumé

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.

Identifiants

pubmed: 35806185
pii: ijms23137185
doi: 10.3390/ijms23137185
pmc: PMC9266429
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Israel Academy of Science and Humanities
ID : 1180/20

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Auteurs

Kesem Nahum (K)

Department of Psychology Experimental Psychology, Brain and Cognition, Faculty of Humanities and Social Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel.

Doron Todder (D)

Beer-Sheva Mental Health Center, Ministry of Health, Anxiety and Stress Research Unit, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8461144, Israel.

Joseph Zohar (J)

Post-Trauma Center, Sheba Medical Center, Tel Aviv University, Tel Aviv 52621, Israel.

Hagit Cohen (H)

Department of Psychology Experimental Psychology, Brain and Cognition, Faculty of Humanities and Social Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel.
Beer-Sheva Mental Health Center, Ministry of Health, Anxiety and Stress Research Unit, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8461144, Israel.
Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel.

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Classifications MeSH