Gene expression changes in the hypothalamus provide evidence for regionally-selective changes in IL-1 and microglial markers after acute stress
Abstract
Recent work from our laboratory and others has shown that certain stressors increase expression of the pro-inflammatory cytokine interleukin-1beta (IL-1) in the hypothalamus. The first goal of the following studies was to assess the impact of acute stress on other key inflammatory factors, including both cytokines and cell surface markers for immune-derived cells resident to the CNS in adult male Sprague Dawley rats exposed to intermittent footshock (80 shocks, 90 s variable ITI, 5 s each). While scattered changes in IL-6 and GFAP were observed in the hippocampus and cortex, we found the hypothalamus to be exquisitely sensitive to the effects of footshock. At the level of the hypothalamus, mRNA for IL-1 and CD14 were significantly increased, while at the same time CD200R mRNA was significantly decreased. A subsequent experiment demonstrated that propranolol (20mg/kg i.p.) blocked the increase in IL-1 and CD14 mRNA observed in the hypothalamus, while the decrease in CD200R was unaffected by propranolol. Interestingly, inhibition of glucocorticoid synthesis via injection of metyrapone (50mg/kg s.c.) plus aminoglutethimide (100mg/kg s.c.) increased basal IL-1 mRNA and augmented IL-1 and CD14 expression provoked by footshock. Injection of minocycline, a putative microglial inhibitor, blocked the IL-1 response to footshock, while CD14 and CD200R were unaffected. Together, these gene expression changes (i) provide compelling evidence that stress may provoke neuroinflammatory changes that extend well beyond isolated changes in a single cytokine; (ii) suggest opposing roles for classic stress-responsive factors (norepinephrine and corticosterone) in the modulation of stress-related neuroinflammation; (iii) indicate microglia within the hypothalamus may be key players in stress-related neuroinflammation; and (iv) provide a potential mechanism (increased CD14) by which acute stress primes reactivity to later immune challenge.
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Restraint stress and other physical stressors induce inflammatory mediators, reduce immunoregulatory proteins, and trigger microglia proliferation in the rodent brain.
“In support of this hypothesis, restraint stress and other physical stressors were shown to induce inflammatory mediators (e.g., iNOS, TNF-α, COX-2, PGE2, IL-1β, and CD14), reduce immunoregulatory proteins (e.g., CD200R) and trigger microglia proliferation in the rodent brain (147–152).”
From The HPA – Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain (2014) · cites this paper as [147]
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- Authors
- Blandino, P., Barnum, C. J., Solomon, L. G., Larish, Y., Lankow, B. S., & Deak, T.
- Affiliations
- Binghamton University (US)
- Venue
- Brain Behavior and Immunity
- Publisher
- Elsevier BV
- Published
- 2009-10
- Volume
- 23
- Issue
- 7
- Pages
- 958-968
- ISSN
- 0889-1591 (ISSN-L)
- OpenAlex
- W2133151251
- Cited by
- 137
- References
- 58
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 5 · 2023: 2 · 2022: 4 · 2021: 3 · 2020: 6 · 2019: 16 · 2018: 9 · 2017: 15 · 2016: 11 · 2015: 12 · 2014: 13 · 2013: 5 · 2012: 7
- FWCI
- 3.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation
- Hope for Depression Research Foundation
- Foundation of Hope for Research and Treatment of Mental Illness
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- acute stress, hypothalamus, neuroinflammation, IL-1β, microglia, CD14, CD200R, propranolol, metyrapone, aminoglutethimide, minocycline, norepinephrine, corticosterone, glucocorticoids, interleukin-6, glial fibrillary acidic protein, footshock
- MeSH terms
- Adrenergic beta-Antagonists, Analysis of Variance, Animals, Cerebral Cortex, Corticosterone, Electroshock, Enzyme Inhibitors, Hippocampus, Hypothalamus, Interleukin-1, Male, Metyrapone, Minocycline, Neurons, Propranolol, Radioimmunoassay, Receptors, Adrenergic, beta, RNA, Messenger, Stress, Physiological, Gene Expression, Rats, Sprague-Dawley, Microglia, Lipopolysaccharide Receptors, Reverse Transcriptase Polymerase Chain Reaction, Rats
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