Neonatal Inflammation Sex‐dependently Impairs Adult, Spinal Microglia

Neonatal inflammation is common and disrupts adult respiratory control, yet the mechanism(s) underlying the impairments are not well understood. Since microglia are key mediators of central inflammation and are important in the lasting effects of neonatal inflammation in non‐respiratory brain regions, we hypothesized lasting dysfunction in microglia underlie impairments in adult respiratory control. Specifically, we hypothesized neonatal inflammation would increase the number of and inflammatory gene expression in adult microglia. Since adult respiratory motor plasticity in the cervical spinal cord is impaired after neonatal inflammation, we analyzed immunomagnetically isolated microglia from the ventral cervical spinal cord. Interestingly, the number of microglia measured by flow cytometry calibrated with counting beads from adults after neonatal inflammation (LPS; 1 mg/kg, i.p.; postnatal day 4) were unchanged in males (LPS: 14,488 ± 4000, n=4; saline: 12,784 ± 4000, n=4, p=0.97) or females (LPS: 14,611 ± 4500, n=4; saline: 9,062 ± 4500, n=5, p=0.79). Additionally, the number of microglia was not significantly different between males and females (p>0.05). Despite no changes in microglia number, we hypothesized microglia function was impaired by neonatal inflammation. Preliminary transcriptomic analysis suggests neonatal inflammation in adult females (n=2) up‐regulated 7 genes and down‐regulated 1 gene, and in adult males (n=3) down‐regulated 1 gene. Gene ontology revealed these differentially expressed genes are associated with inflammatory signaling. While neonatal inflammation has no impact on the number of microglia, it sex‐dependently increases inflammatory‐related gene expression in females with surprisingly few changes in adult males. Thus, adult, female microglia likely contribute to the lasting impairments in respiratory control following neonatal inflammation. Further, the lasting impairments in adult males are likely mediated by a sex‐specific distinct mechanism. Understanding the sex‐specific inflammatory mechanisms impairing respiratory control is crucial to developing treatment strategies to promote breathing during ventilatory control disorders. Support or Funding Information Supported by NIH HL141249 (AGH)