Neuropeptide Y protects cerebral cortical neurons by regulating microglial immune function

Neuropeptide Y has been shown to inhibit the immunological activity of reactive microglia in the rat cerebral cortex, to reduce N-methyl-D-aspartate current (I-NMDA) in cortical neurons, and protect neurons. In this study, after primary cultured microglia from the cerebral cortex of rats were treated with lipopolysaccharide, interleukin-1 beta and tumor necrosis factor-a levels in the cell culture medium increased, and mRNA expression of these cytokines also increased. After primary cultured cortical neurons were incubated with the lipopolysaccharide-treated microglial conditioned medium, peak I-NMDA in neurons increased. These effects of lipopolysaccharide were suppressed by neuropeptide Y. After addition of the neuropeptide YY1 receptor antagonist BIBP3226, the effects of neuropeptide Y completely disappeared. These results suggest that neuropeptide Y prevents excessive production of interleuldn-1 beta and tumor necrosis factor-alpha by inhibiting microglial reactivity. This reduces I-NMDA in rat cortical neurons, preventing excitotoxicity, thereby protecting neurons.