Neonatal lipopolysaccharide exposure alters steroid regulation and gene expression in the adult mouse brain

Early-life infections during development can have enduring consequences on brain development and function. The mechanisms underlying how illness in early life programs the brain are unknown. Bacterial infections activate the hypothalamic-pituitary-adrenal (HPA) axis and increase glucocorticoid (GC) and mineralocorticoid (MC) secretion from the adrenal glands. Exposure to lipopolysaccharide (LPS), an endotoxin found in Gram-negative bacteria, at postnatal day (PND) 5 also induces GC production in the mouse brain. GCs can act as transcription factors to promote or supress thousands of genes. It is unclear whether neonatal LPS administration (“1st hit”) alters GC and MC regulation, and gene expression, in the mouse brain after adult LPS administration (“2nd hit”). Here, male and female C57BL/6J mice were injected intraperitoneally with saline (vehicle control) or 50ug/kg LPS at PND 4 and 6 (“1st hit”). Mice were injected again with either saline or 50ug/kg LPS in adulthood (“2nd hit) (2x2 design). The brain and blood were collected 4 hr after adult treatment (n=10/sex/group). We microdissected the dorsal hippocampus and conducted mRNA sequencing.