Metabolic trade-offs in Neonatal sepsis triggered by TLR4 and TLR1/2 ligands result in unique dysfunctions in neural breathing circuits.

ABSTRACT: Neonatal sepsis remains one of the leading causes of mortality in newborns. Several brainstem-regulated physiological processes undergo disruption during neonatal sepsis. Mechanistic knowledge gaps exist at the interplay between metabolism and immune activation to brainstem neural circuits and pertinent physiological functions in neonates. To delineate this association, we induced systemic inflammation either by TLR4 (LPS) or TLR1/2 (PAM3CSK4) ligand administration in postnatal day 5 mice (PD5). Our findings show that LPS and PAM3CSK4 evoke substantial changes in respiration and metabolism. Physiological trade-offs led to hypometabolic-hypothermic responses due to LPS, but not PAM3CSK4, whereas to both TLR ligands blunted respiratory chemoreflexes. Neuroinflammatory pathways modulation in

SUBMITTER: Joana Alves M 

PROVIDER: S-EPMC12128324 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature