Acute stress induces chronic neuroinflammatory,microglial and behavioral priming: A role for potentiated NLRP3 inflammasome activation |
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| Institution: | 1. Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80301, USA;2. Division of Pharmacology and Toxicology, University of Texas at Austin, Austin, TX 78712, USA;1. Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO 80301, USA;2. Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80301, USA;3. Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA 22908, USA;1. Department of Anesthesiology, Weill Cornell Medicine, New York, New York;2. Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York;3. Norris Medical Library, University of Southern California, Los Angeles, California;4. Department of Psychiatry and Neurosciences, Laval University, Québec, Québec, Canada;1. Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, 3330 Hospital Dr. NW, Calgary, AB T2N 4N1, Canada;2. Mathison Centre for Mental Health Research and Education, Cumming School of Medicine, University of Calgary, 3330 Hospital Dr. NW, Calgary, AB T2N 4N1, Canada;3. Department of Neuroscience, Cumming School of Medicine, University of Calgary, 3330 Hospital Dr. NW, Calgary, AB T2N 4N1, Canada;4. Department of Cell Biology and Anatomy, Cumming School of Medicine, University of Calgary, 3330 Hospital Dr. NW, Calgary, AB T2N 4N1, Canada;5. Department of Psychiatry, Cumming School of Medicine, University of Calgary, 3330 Hospital Dr. NW, Calgary, AB T2N 4N1, Canada |
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| Abstract: | Prior exposure to acute and chronic stressors potentiates the neuroinflammatory and microglial pro-inflammatory response to subsequent immune challenges suggesting that stressors sensitize or prime microglia. Stress-induced priming of the NLRP3 inflammasome has been implicated in this priming phenomenon, however the duration/persistence of these effects has not been investigated. In the present study, we examined whether exposure to a single acute stressor (inescapable tailshock) induced a protracted priming of the NLRP3 inflammasome as well as the neuroinflammatory, behavioral and microglial proinflammatory response to a subsequent immune challenge in hippocampus. In male Sprague-Dawley rats, acute stress potentiated the neuroinflammatory response (IL-1β, IL-6, and NFκBIα) to an immune challenge (lipopolysaccharide; LPS) administered 8 days after stressor exposure. Acute stress also potentiated the proinflammatory cytokine response (IL-1β, IL-6, TNF and NFκBIα) to LPS ex vivo. This stress-induced priming of microglia also was observed 28 days post-stress. Furthermore, challenge with LPS reduced juvenile social exploration, but not sucrose preference, in animals exposed to stress 8 days prior to immune challenge. Exposure to acute stress also increased basal mRNA levels of NLRP3 and potentiated LPS-induction of caspase-1 mRNA and protein activity 8 days after stress.The present findings suggest that acute stress produces a protracted vulnerability to the neuroinflammatory effects of subsequent immune challenges, thereby increasing risk for stress-related psychiatric disorders with an etiological inflammatory component.Further, these findings suggest the unique possibility that acute stress might induce innate immune memory in microglia. |
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| Keywords: | Stress Neuroinflammation Inflammasome NLRP3 Priming Microglia |
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