Early-life adversity programs long-term cytokine and microglia expression within the HPA axis in female Japanese quail.

Abstract

Stress exposure during pre and post-natal development can have persistent and often dysfunctional effects on several physiological systems, including immune function, affecting the ability to combat infection. The neuro-immune response is inextricably linked to the action of the Hypothalamic Pituitary Adrenal (HPA) axis. Cytokines released from neuro-immune cells, including microglia, activate the HPA axis while glucocorticoids in turn regulate cytokine release from microglia. Because of the close links between these two physiological systems, coupled with potential for persistent changes to HPA axis activity following developmental stress, components of the neuro-immune system could be targets for developmental programming. However, little is known of any programming effects of developmental stress on neuro-immune function. We investigated whether developmental stress exposure via elevated pre-natal corticosterone (CORT) or post-natal unpredictable food availability, had long-term effects on pro (IL-1β) and anti-inflammatory (IL-10) cytokine and microglia-dependent gene (CSF1R) expression within HPA axis tissues in a precocial bird, the Japanese quail (Coturnix japonica). Following post-natal stress, we observed increased IL-1β expression in the pituitary gland, reduced IL-10 expression in the amygdala and hypothalamus and reduced CSF1R expression within the hypothalamus and pituitary gland. Post-natal stress disrupted the ratio of IL-1β:IL-10 expression within the hippocampus and hypothalamus. Pre-natal stress only increased IL-1β expression in the pituitary gland. We found no evidence for interactive or cumulative effects across life stages on basal cytokine and glia expression in adulthood. We show that post-natal stress may have a larger impact than elevated pre-natal CORT on basal immunity in HPA axis specific brain regions, with changes in cytokine homeostasis and microglia abundance. These results provide evidence for post-natal programming of a pro-inflammatory neuro-immune phenotype at the expense of reduced microglia, which could have implications for CNS health and subsequent neuro-immune responses.