Interleukin-1β Disturbs the Proliferation and Differentiation of Neural Precursor Cells in the Hippocampus via Activation of Notch Signaling in Postnatal Rats Exposed to Lipopolysaccharide

Infectious exposure during the perinatal period may predispose to permanent neurological disorders in later life. Here we investigated whether changes in interleukin-1β (IL-1β) are associated with cognitive dysfunction in later life of septic neonatal rats through suppression of neurogenesis in the hippocampus. Sprague–Dawley rats (1-day old) administered lipopolysaccharide (LPS) showed upregulated expression of IL-1β and IL-1 receptors in the hippocampus. At 28 days of age, rats showed longer escape latencies and decreased numbers of crossings after LPS administration. This was coupled with increased numbers of glial fibrillary acidic protein positive (GFAP+) astrocytes and decreased numbers of neuronal nuclei positive (NeuN+) cells. The numbers of sex-determining region Y-box 2 positive (SOX2+) and doublecortin positive (DCX+) cells were decreased at 1 and 3 days but was increased at 7 and 14 days. The proliferation of SOX2+ cells was inhibited at 1 and 3 days but increased at 7 and 14 days. In vitro IL-1β administration suppressed the proliferation of neural progenitor cells (NPCs) in neurospheres derived from the hippocampus. GFAP expression was upregulated in differentiated NPCs treated with IL-1β for 4 days, but expression of DCX and microtubule associated protein-2 (MAP2) was decreased. Remarkably, the Notch signaling pathway involved in antineurogenic and progliogenic differentiation of NPCs was activated after IL-1β administration. The results show that following LPS injection in neonatal rats, microglia were activated and generated excess amounts of IL-1β in the hippocampus. It is suggested that this might have contributed to inhibiting neurogenesis but promoting gliogenesis of NPCs via activation of the Notch signaling pathway and maybe one of the causes for cognitive dysfunction in septic neonatal rats in later life.