4.5 Article

Phenotypic characterization of frontal cortex microglia in a rat model of post-traumatic stress disorder

Journal

BRAIN AND BEHAVIOR
Volume 11, Issue 3, Pages -

Publisher

WILEY
DOI: 10.1002/brb3.2011

Keywords

Fear Extinction; Microglia; Post-traumatic Stress Disorder; PTSD; Rat; Single Prolonged Stress; SPS

Funding

  1. U.S. Department of Defense

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Psychological trauma alters the expression of pro-inflammatory and anti-inflammatory markers in microglia, as shown in a rat model study. Fear conditioning and extinction experiments further demonstrate the impact of trauma on fear resolution and immunological phenotype. Future research should focus on understanding the mechanistic role of microglia in PTSD pathology.
Introduction: Post-traumatic stress disorder (PTSD) is an anxiety disorder induced by psychologically traumatic events. Using a rat model, this study aimed to determine whether psychological trauma alters relative expression between pro-inflammatory and anti-inflammatory markers in microglia. To meet this goal, expression of genes encoding i-NOS, arginase, TNF-alpha, interleukin-10, CD74, and Mannose Receptor C was analyzed on multiple days following trauma exposure. Methods: Single-prolonged stress (SPS) was used to model PTSD in male Sprague-Dawley rats. Twenty-four rats (12 Controls and 12 SPS-exposed) were sacrificed on Days 1, 3, and 7 post-SPS. Twenty-four (12 Controls and 12 SPS-exposed) additional rats were exposed to classical fear conditioning on Day 7, and fear extinction on Days 8, 9, 10, 15, 16, and 17. Freezing behavior was measured to assess fear resolution. Microglial isolates were collected from the frontal cortex, and RNA was extracted. Changes in relative expression of target genes were quantified via RT-PCR. Results: SPS rats showed significant decreases in IL-10 and TNF-alpha expression and increases in the i-NOS:Arginase and TNF-alpha:IL-10 ratios compared to Controls on Day 1, but not on Day 3 or Day 7 for any of the dependent variables. Day 17 SPS rats showed a significant decrease in IL-10 expression and an increase in the TNF-alpha:IL-10 ratio, further characterized by a significant inverse relationship between IL-10 expression and fear persistence. Conclusion: Psychological trauma impacts the immunological phenotype of microglia of the frontal cortex. Consequently, future studies should further evaluate the mechanistic role of microglia in PTSD pathology.

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