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Sci Rep. 2018 Jul 26;8(1):11240. doi: 10.1038/s41598-018-28737-8.

Decoding microglia responses to psychosocial stress reveals blood-brain barrier breakdown that may drive stress susceptibility.

Author information

1
Section on Functional Neuroanatomy, Intramural Research Program, National Institute of Mental Health, NIH, Bethesda, MD, 20892, USA. michael.lehmann@nih.gov.
2
Section on Functional Neuroanatomy, Intramural Research Program, National Institute of Mental Health, NIH, Bethesda, MD, 20892, USA.
3
Division of Intramural Research Programs Microarray Core Facility, National Institutes of Health, Bethesda, MD, 20892, USA.

Abstract

An animal's ability to cope with or succumb to deleterious effects of chronic psychological stress may be rooted in the brain's immune responses manifested in microglial activity. Mice subjected to chronic social defeat (CSD) were categorized as susceptible (CSD-S) or resilient (CSD-R) based on behavioral phenotyping, and their microglia were isolated and analyzed by microarray. Microglia transcriptomes from CSD-S mice were enriched for pathways associated with inflammation, phagocytosis, oxidative stress, and extracellular matrix remodeling. Histochemical experiments confirmed the array predictions: CSD-S microglia showed elevated phagocytosis and oxidative stress, and the brains of CSD-S but not CSD-R or non-stressed control mice showed vascular leakage of intravenously injected fluorescent tracers. The results suggest that the inflammatory profile of CSD-S microglia may be precipitated by extracellular matrix degradation, oxidative stress, microbleeds, and entry and phagocytosis of blood-borne substances into brain parenchyma. We hypothesize that these CNS-centric responses contribute to the stress-susceptible behavioral phenotype.

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