Ovarian status dictates the neuroinflammatory and behavioral consequences of sub-chronic stress exposure in middle-aged female mice
Ovarian hormones influence the outcomes of stress exposure and are implicated in stress-related disorders including depression, yet their roles are often complex and seemingly contradictory. Importantly, depression and stress exposure are associated with immune dysregulation, and ovarian hormones ha...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-05-01
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| Series: | Neurobiology of Stress |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352289519300517 |
| _version_ | 1818537497561399296 |
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| author | Rand S. Eid Stephanie E. Lieblich Sarah J. Wong Liisa A.M. Galea |
| author_facet | Rand S. Eid Stephanie E. Lieblich Sarah J. Wong Liisa A.M. Galea |
| author_sort | Rand S. Eid |
| collection | DOAJ |
| description | Ovarian hormones influence the outcomes of stress exposure and are implicated in stress-related disorders including depression, yet their roles are often complex and seemingly contradictory. Importantly, depression and stress exposure are associated with immune dysregulation, and ovarian hormones have immunomodulatory properties. However, how ovarian hormones can influence the inflammatory outcomes of stress exposure is poorly understood. Here, we examined the effects of long-term ovariectomy on the behavioral and neuroinflammatory outcomes of sub-chronic stress exposure in middle-aged mice. Briefly, sham-operated and ovariectomized mice were assigned to non-stress groups or exposed to 6 days of variable stress. Mice were assessed on a battery of behavioral tests, and cytokine concentrations were quantified in the frontal cortex and hippocampus. In the frontal cortex, postsynaptic density protein-95 expression was examined as an index of excitatory synapse number and/or stability, and phosphorylated mitogen-activated protein kinases (MAPKs) were measured to explore potential cell signaling pathways elicited by stress exposure and/or ovarian hormones. Long-term ovariectomy modified the central cytokine profile by robustly reducing cytokine concentrations in the frontal cortex and modestly increasing concentrations in the hippocampus. Under non-stress conditions, long-term ovariectomy also reduced extracellular signal-regulated kinase (ERK) phosphoprotein expression in the frontal cortex and increased some measures of depressive-like behavior. The effects of sub-chronic stress exposure were however more pronounced in sham-operated mice. Notably, in sham-operated mice only, sub-chronic stress exposure increased IL-1β and IL-6:IL-10 ratio in the frontal cortex and hippocampus and reduced pERK1/2 expression in the frontal cortex. Further, although sub-chronic stress exposure increased anhedonia-like behavior regardless of ovarian status, it increased passive-coping behavior in sham-operated mice only. These data indicate that long-term ovariectomy has potent effects on the central cytokine milieu and dictates the neuroinflammatory and behavioral effects of sub-chronic stress exposure in middle-aged mice. These findings therefore suggest that the immunomodulatory properties of ovarian hormones are of relevance in the context of stress and possibly depression. |
| first_indexed | 2024-12-11T18:51:30Z |
| format | Article |
| id | doaj.art-865990d3d4fb4bb2bd20cec6b4e110fc |
| institution | Directory Open Access Journal |
| issn | 2352-2895 |
| language | English |
| last_indexed | 2024-12-11T18:51:30Z |
| publishDate | 2020-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Stress |
| spelling | doaj.art-865990d3d4fb4bb2bd20cec6b4e110fc2022-12-22T00:54:16ZengElsevierNeurobiology of Stress2352-28952020-05-0112Ovarian status dictates the neuroinflammatory and behavioral consequences of sub-chronic stress exposure in middle-aged female miceRand S. Eid0Stephanie E. Lieblich1Sarah J. Wong2Liisa A.M. Galea3Graduate Program in Neuroscience, University of British Columbia, Vancouver, BC, Canada; Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, CanadaDepartment of Psychology, University of British Columbia, Vancouver, BC, Canada; Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, CanadaDepartment of Psychology, University of British Columbia, Vancouver, BC, Canada; Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, CanadaGraduate Program in Neuroscience, University of British Columbia, Vancouver, BC, Canada; Department of Psychology, University of British Columbia, Vancouver, BC, Canada; Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada; Corresponding author. Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 2215 Wesbrook Mall, Vancouver, BC, V6T 1Z3, Canada.Ovarian hormones influence the outcomes of stress exposure and are implicated in stress-related disorders including depression, yet their roles are often complex and seemingly contradictory. Importantly, depression and stress exposure are associated with immune dysregulation, and ovarian hormones have immunomodulatory properties. However, how ovarian hormones can influence the inflammatory outcomes of stress exposure is poorly understood. Here, we examined the effects of long-term ovariectomy on the behavioral and neuroinflammatory outcomes of sub-chronic stress exposure in middle-aged mice. Briefly, sham-operated and ovariectomized mice were assigned to non-stress groups or exposed to 6 days of variable stress. Mice were assessed on a battery of behavioral tests, and cytokine concentrations were quantified in the frontal cortex and hippocampus. In the frontal cortex, postsynaptic density protein-95 expression was examined as an index of excitatory synapse number and/or stability, and phosphorylated mitogen-activated protein kinases (MAPKs) were measured to explore potential cell signaling pathways elicited by stress exposure and/or ovarian hormones. Long-term ovariectomy modified the central cytokine profile by robustly reducing cytokine concentrations in the frontal cortex and modestly increasing concentrations in the hippocampus. Under non-stress conditions, long-term ovariectomy also reduced extracellular signal-regulated kinase (ERK) phosphoprotein expression in the frontal cortex and increased some measures of depressive-like behavior. The effects of sub-chronic stress exposure were however more pronounced in sham-operated mice. Notably, in sham-operated mice only, sub-chronic stress exposure increased IL-1β and IL-6:IL-10 ratio in the frontal cortex and hippocampus and reduced pERK1/2 expression in the frontal cortex. Further, although sub-chronic stress exposure increased anhedonia-like behavior regardless of ovarian status, it increased passive-coping behavior in sham-operated mice only. These data indicate that long-term ovariectomy has potent effects on the central cytokine milieu and dictates the neuroinflammatory and behavioral effects of sub-chronic stress exposure in middle-aged mice. These findings therefore suggest that the immunomodulatory properties of ovarian hormones are of relevance in the context of stress and possibly depression.http://www.sciencedirect.com/science/article/pii/S2352289519300517Ovarian hormonesStressDepressive-like behaviorCytokinesMAPKsPSD-95 |
| spellingShingle | Rand S. Eid Stephanie E. Lieblich Sarah J. Wong Liisa A.M. Galea Ovarian status dictates the neuroinflammatory and behavioral consequences of sub-chronic stress exposure in middle-aged female mice Neurobiology of Stress Ovarian hormones Stress Depressive-like behavior Cytokines MAPKs PSD-95 |
| title | Ovarian status dictates the neuroinflammatory and behavioral consequences of sub-chronic stress exposure in middle-aged female mice |
| title_full | Ovarian status dictates the neuroinflammatory and behavioral consequences of sub-chronic stress exposure in middle-aged female mice |
| title_fullStr | Ovarian status dictates the neuroinflammatory and behavioral consequences of sub-chronic stress exposure in middle-aged female mice |
| title_full_unstemmed | Ovarian status dictates the neuroinflammatory and behavioral consequences of sub-chronic stress exposure in middle-aged female mice |
| title_short | Ovarian status dictates the neuroinflammatory and behavioral consequences of sub-chronic stress exposure in middle-aged female mice |
| title_sort | ovarian status dictates the neuroinflammatory and behavioral consequences of sub chronic stress exposure in middle aged female mice |
| topic | Ovarian hormones Stress Depressive-like behavior Cytokines MAPKs PSD-95 |
| url | http://www.sciencedirect.com/science/article/pii/S2352289519300517 |
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