title: Divergent responses of inflammatory mediators within the amygdala and medial prefrontal cortex to acute psychological stress.
abstract: There is now a growing body of literature that indicates that stress can initiate inflammatory processes, both in the periphery and brain; however, the spatiotemporal nature of this response is not well characterized. The aim of this study was to examine the effects of an acute psychological stress on changes in mRNA and protein levels of a wide range of inflammatory mediators across a broad temporal range, in key corticolimbic brain regions involved in the regulation of the stress response (amygdala, hippocampus, hypothalamus, medial prefrontal cortex). mRNA levels of inflammatory mediators were analyzed immediately following 30min or 120min of acute restraint stress and protein levels were examined 0h through 24h post-termination of 120min of acute restraint stress using both multiplex and ELISA methods. Our data demonstrate, for the first time, that exposure to acute psychological stress results in an increase in the protein level of several inflammatory mediators in the amygdala while concomitantly producing a decrease in the protein level of multiple inflammatory mediators within the medial prefrontal cortex. This pattern of changes seemed largely restricted to the amygdala and medial prefrontal cortex, with stress producing few changes in the mRNA or protein levels of inflammatory mediators within the hippocampus or hypothalamus. Consistent with previous research, stress resulted in a general elevation in multiple inflammatory mediators within the circulation. These data indicate that neuroinflammatory responses to stress do not appear to be generalized across brain structures and exhibit a high degree of spatiotemporal specificity. Given the impact of inflammatory signaling on neural excitability and emotional behavior, these data may provide a platform with which to explore the importance of inflammatory signaling within the prefrontocortical-amygdala circuit in the regulation of the neurobehavioral responses to stress.
authors.affiliation: Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, 3330 Hospital Dr. NW, Calgary, AB T2N 4N1, Canada; Mathison Centre for Mental Health Research and Education, Cumming School of Medicine, University of Calgary, 3330 Hospital Dr. NW, Calgary, AB T2N 4N1, Canada; Department of Neuroscience, Cumming School of Medicine, University of Calgary, 3330 Hospital Dr. NW, Calgary, AB T2N 4N1, Canada.
authors.forename: Haley A
authors.initials: HA
authors.lastname: Vecchiarelli
authors.affiliation: Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, 3330 Hospital Dr. NW, Calgary, AB T2N 4N1, Canada; Mathison Centre for Mental Health Research and Education, Cumming School of Medicine, University of Calgary, 3330 Hospital Dr. NW, Calgary, AB T2N 4N1, Canada; Department of Neuroscience, Cumming School of Medicine, University of Calgary, 3330 Hospital Dr. NW, Calgary, AB T2N 4N1, Canada.
authors.forename: Chaitanya P
authors.initials: CP
authors.lastname: Gandhi
authors.affiliation: Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, 3330 Hospital Dr. NW, Calgary, AB T2N 4N1, Canada; Mathison Centre for Mental Health Research and Education, Cumming School of Medicine, University of Calgary, 3330 Hospital Dr. NW, Calgary, AB T2N 4N1, Canada; Department of Cell Biology and Anatomy, Cumming School of Medicine, University of Calgary, 3330 Hospital Dr. NW, Calgary, AB T2N 4N1, Canada.
authors.forename: J Megan
authors.initials: JM
authors.lastname: Gray
authors.affiliation: Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, 3330 Hospital Dr. NW, Calgary, AB T2N 4N1, Canada; Mathison Centre for Mental Health Research and Education, Cumming School of Medicine, University of Calgary, 3330 Hospital Dr. NW, Calgary, AB T2N 4N1, Canada; Department of Cell Biology and Anatomy, Cumming School of Medicine, University of Calgary, 3330 Hospital Dr. NW, Calgary, AB T2N 4N1, Canada.
authors.forename: Maria
authors.initials: M
authors.lastname: Morena
authors.affiliation: Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, 3330 Hospital Dr. NW, Calgary, AB T2N 4N1, Canada; Mathison Centre for Mental Health Research and Education, Cumming School of Medicine, University of Calgary, 3330 Hospital Dr. NW, Calgary, AB T2N 4N1, Canada.
authors.forename: Kowther I
authors.initials: KI
authors.lastname: Hassan
authors.affiliation: Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, 3330 Hospital Dr. NW, Calgary, AB T2N 4N1, Canada; Mathison Centre for Mental Health Research and Education, Cumming School of Medicine, University of Calgary, 3330 Hospital Dr. NW, Calgary, AB T2N 4N1, Canada; Department of Cell Biology and Anatomy, Cumming School of Medicine, University of Calgary, 3330 Hospital Dr. NW, Calgary, AB T2N 4N1, Canada; Department of Psychiatry, Cumming School of Medicine, University of Calgary, 3330 Hospital Dr. NW, Calgary, AB T2N 4N1, Canada. Electronic address: mnhill@ucalgary.ca.
authors.forename: Matthew N
authors.initials: MN
authors.lastname: Hill
mesh_terms: D000679:Amygdala / Q000378:metabolism*; D000818:Animals; D006624:Hippocampus / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D017397:Prefrontal Cortex / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000378:metabolism*; D013997:Time Factors
chemical_list: D018836:Inflammation Mediators; D012333:RNA, Messenger
keywords: Amygdala; Cytokine; Interleukin; Medial prefrontal cortex; Psychological stress; TNF