Autonomic regions of the brainstem show a sex-specific inflammatory response to systemic neonatal lipopolysaccharide

Abstract Early life inflammation has been linked to long-term deficits in the central nervous system in relation to behavioural disorders, but it is now becoming more apparent it can also lead to autonomic dysfunction. The brainstem contains all critical control centres for autonomic homeostasis, so we used the well-established model of neonatal lipopolysaccharide (LPS) exposure to examine the immediate and long-term impacts of systemic inflammation on the autonomic regions of the brainstem. Wistar rats were injected with LPS or saline on postnatal days 3 and 5, with sacrifices made on postnatal days 7 and 90. At both timepoints inflammatory mediators were assessed in the brainstem via RT-qPCR and microglia were characterised by immunofluorescence in the autonomic regions of the brainstem. In the brainstem there was a distinct sex-specific response of all measured inflammatory mediators at both ages, as well as significant neonatal sex differences in inflammatory mediators at baseline. AT both ages, microglial morphology had a significant change to branch length and soma size in a sex-specific manner, which strongly indicate a significant effect of neonatal immune activation. This data not only highlights the strong sex-specific response of neonates to LPS administration, but also the significant impact on the brainstem in adulthood.