Abstract
<title>Abstract</title> <p> Background Early-life infection is a major environmental risk factor for impaired brain development, yet the mechanisms linking neonatal infection to disrupted neurodevelopment remain poorly understood. <italic>Staphylococcus epidermidis (SE)</italic> , a leading cause of neonatal sepsis, may influence developmental signaling through neuronal primary cilia, sensory organelles that regulate multiple pathways essential for brain maturation. We investigated whether neonatal <italic>SE</italic> infection alters neuronal primary cilia and cilia-associated signaling networks in the developing hippocampus. Methods Hippocampal proteomic data from male mice 24 h after neonatal <italic>SE</italic> infection (PND5) were re-analyzed to identify cilia-associated proteins and pathways. Moreover, stereological quantification of neuronal primary cilia in hippocampal subregions was performed. Results <italic>SE</italic> infection induced coordinated remodeling of cilia-associated protein networks, characterized by altered expression of proteins involved in ciliary structure, cytoskeletal organization, and developmental signaling. Pathway analyses identified dysregulation of Hedgehog, Wnt, BMP/TGF-β, PKA/CREB, PDGF, and mTOR signaling. Structurally, <italic>SE</italic> infection increased neuronal primary cilia density in the CA1 and CA3 pyramidal layers without affecting cilia length, although region-specific alterations in the upper distribution of cilia lengths were detected. Conclusions These findings identify primary cilia as a sensitive target of early-life inflammation and provide a potential mechanistic link between neonatal infection and altered hippocampal development. </p>