Dataset Information

Acute Stress, Induced by IFNγ + Aβ, and Chronic Stress, Induced by Age, Affect Microglia in a Sex-Specific Manner.

ABSTRACT: Microglial phenotype changes in the aged brain, and also in neurodegenerative diseases, and it is generally accepted that these changes at least contribute to the inflammation that can have detrimental effects on brain health. Accumulating data have determined that there are multiple microglial activation states with consistent findings indicating that with stressors including age, a switch towards an inflammatory phenotype occurs. Among the changes that accompany this is a change in metabolism, whereby glycolysis is increased in microglia. Here, we asked whether sex impacted on the response of microglia to two stressors, interferon-γ + amyloid-β (IFNγ + Aβ) and age. The data show that IFNγ + Aβ triggered cells from female mice to adopt a glycolytic phenotype. Metabolism was also altered with age; microglia from aged male mice responded by increasing oxidative phosphorylation, and microglial motility was preserved, contrasting with microglia from female mice where motility was compromised. We conclude that sex is a significant variable in the responses of microglia to stressors.

SUBMITTER: Mela V

PROVIDER: S-EPMC10122617 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Acute Stress, Induced by IFNγ + Aβ, and Chronic Stress, Induced by Age, Affect Microglia in a Sex-Specific Manner.

Mela Virginia V Gaban Aline Sayd AS Shatz Paul Marie PM Guillot-Sestier Marie-Victoire MV Lynch Marina A MA

Molecular neurobiology 20230214 6

Microglial phenotype changes in the aged brain, and also in neurodegenerative diseases, and it is generally accepted that these changes at least contribute to the inflammation that can have detrimental effects on brain health. Accumulating data have determined that there are multiple microglial activation states with consistent findings indicating that with stressors including age, a switch towards an inflammatory phenotype occurs. Among the changes that accompany this is a change in metabolism, ...[more]

PMID: 36781739

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Project description:Women are more susceptible to numerous stress-linked psychological disorders (e.g., depression) characterized by dysfunction of corticolimbic brain regions critical for emotion regulation and cognitive function. Although sparsely investigated, a number of studies indicate sex differences in stress effects on neuronal structure, function, and behaviors associated with these regions. We recently demonstrated a basal sex difference in- and differential effects of stress on- microglial activation in medial prefrontal cortex (mPFC). The resident immune cells of the brain, microglia are implicated in synaptic and dendritic plasticity, and cognitive-behavioral function. Here, we examined the effects of acute (3h/day, 1 day) and chronic (3h/day, 10 days) restraint stress on microglial density and morphology, as well as immune factor expression in orbitofrontal cortex (OFC), basolateral amygdala (BLA), and dorsal hippocampus (DHC) in male and female rats. Microglia were visualized, classified based on their morphology, and stereologically counted. Microglia-associated transcripts (CD40, iNOS, Arg1, CX3CL1, CX3CR1, CD200, and CD200R) were assessed in brain punches from each region. Expression of genes linked with cellular stress, neuroimmune state, and neuron-microglia communication varied between unstressed male and female rats in a region-specific manner. In OFC, chronic stress upregulated a wider variety of immune factors in females than in males. Acute stress increased microglia-associated transcripts in BLA in males, whereas chronic stress altered immune factor expression in BLA more broadly in females. In DHC, chronic stress increased immune factor expression in males but not females. Moreover, acute and chronic stress differentially affected microglial morphological activation state in male and female rats across all brain regions investigated. In males, chronic stress altered microglial activation in a pattern consistent with microglial involvement in stress-induced dendritic remodeling across OFC, BLA, and DHC. Together, these data suggest the potential for microglia-mediated sex differences in stress effects on neural structure, function, and behavior.

Dataset Information

Acute Stress, Induced by IFNγ + Aβ, and Chronic Stress, Induced by Age, Affect Microglia in a Sex-Specific Manner.

Publications

Acute Stress, Induced by IFNγ + Aβ, and Chronic Stress, Induced by Age, Affect Microglia in a Sex-Specific Manner.

Similar Datasets

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