Chronic adolescent stress sex-specifically alters central and peripheral neuro-immune reactivity in rats

Autor: Sean D. Kelly, Mandakh Bekhbat, Sydney A. Rowson, Gretchen N. Neigh, Malú G. Tansey, Paul Howell
Rok vydání: 2019
Předmět:
Central Nervous System
Lipopolysaccharides
Male
0301 basic medicine
medicine.medical_treatment
Interleukin-1beta
Pituitary-Adrenal System
Hippocampus
Anxiety
Hippocampal formation
Behavioral Neuroscience
chemistry.chemical_compound
0302 clinical medicine
Corticosterone
Depression
Age Factors
NF-kappa B
Anxiety Disorders
Cytokine
Cytokines
Female
medicine.symptom
Hypothalamo-Hypophyseal System
medicine.medical_specialty
Neuroimmunomodulation
Immunology
Inflammation
Article
03 medical and health sciences
Receptors
Glucocorticoid
Sex Factors
Immune system
Internal medicine
medicine
Animals
Rats
Wistar
Neuroinflammation
Depressive Disorder
Innate immune system
Endocrine and Autonomic Systems
business.industry
Rats
030104 developmental biology
Endocrinology
chemistry
business
Metabolism
Inborn Errors
Stress
Psychological
030217 neurology & neurosurgery
Zdroj: Brain, Behavior, and Immunity. 76:248-257
ISSN: 0889-1591
Popis: Adversity during development is a reliable predictor of psychiatric disorders such as depression and anxiety which are increasingly recognized to have an immune component. We have previously demonstrated that chronic adolescent stress (CAS) in rats leads to depressive-like behavior in adulthood along with long-lasting changes to the hypothalamic-pituitary-adrenal axis and pro-inflammatory cytokine induction in the hippocampus. However, the mechanisms by which CAS promotes hippocampal inflammation are not yet defined. Here we tested the hypothesis that a history of CAS exaggerates induction of the pro-inflammatory NFκB pathway in the adult rat hippocampus without compromising the peripheral immune response. We also assessed potential sex differences because it is unclear whether females, who are twice as likely to suffer from mood disorders as males, are disproportionally affected by stress-primed inflammation. Male and female adolescent rats underwent a CAS paradigm or received no stress. Six weeks following the last stressor, all rats received a single systemic injection of either lipopolysaccharide or vehicle to unmask possible immune-priming effects of CAS. An NFκB signaling PCR array demonstrated that CAS exaggerated the expression of NFκB-related genes in the hippocampus of both males and females. Interestingly, targeted qPCR demonstrated that CAS potentiated the induction of hippocampal IL1B and REL mRNA in female rats only, suggesting that some immune effects of CAS are indeed sex-specific. In contrast to the hippocampal findings, indices of peripheral inflammation such as NFκB activity in the spleen, plasma IL-1β, IL-6, TNF-α, and corticosterone were not impacted by CAS in female rats. Despite showing no pro-inflammatory changes to hippocampal mRNA, male CAS rats displayed lower plasma corticosterone response to LPS at 2 h after injection followed by an exaggerated plasma IL-1β response at 4 h. This potentially blunted corticosterone response coupled with excessive innate immune signaling in the periphery is consistent with possible glucocorticoid resistance in males. In contrast, the effects of CAS manifested as excessive hippocampal immune reactivity in females. We conclude that while a history of exposure to chronic adolescent stress enhances adult immune reactivity in both males and females, the mechanism and manifestation of such alterations are sex-specific.
Databáze: OpenAIRE
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