Synaptic structure and alterations in the hippocampus in neonatal rats exposed to lipopolysaccharide

Abstract

Synaptic structure integrity plays a key role in learning and memory. Previous studies have shown that there is cognitive dysfunction in septic neonates in later life. In this study, intraperitoneal injection of lipopolysaccharide (LPS) in the developing rats was used as a sepsis model to determine whether hippocampal synapses would be affected. Expression of synaptophysin (Syn), synaptosomal associated protein of 25 kD (SNAP-25), and N-methyl d-aspartate receptor (NMDAR) in the hippocampus in septic brain were significantly reduced. Consistent with this, the number of dendritic spines associated with the pyramidal neurons in the CA1 region of hippocampus at 28d after LPS administration was decreased. Additionally, the number of synapse and synaptic vesicles were reduced and appeared swollen. The number of neurons in the CA1 and CA3 of hippocampus at 14, and 28d after LPS injection remained unchanged. Coupled with the above was upregulated expression of interleukin-1β (IL-1β), IL-1 receptor 1 (IL-R1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS) at 1-3d after LPS injection. IL-1β expression was specifically detected in activated microglia. The plasma corticosterone (CORT) concentration in the LPS treatment rats was increased; but the glucocorticoid receptor (GR) expression in the hippocampus was decreased. We conclude that LPS injection in neonatal rats can cause synaptic disruption in the hippocampus which may be attributed to inflammatory response due to excess production of proinflammatory cytokines e.g., IL-1β derived from activated microglia. The significance of increased plasma CORT concentration and decreased GR expression in the hippocampus is discussed.