Induction of hippocampal neurogenesis by a tolerogenic peptide that ameliorates lupus manifestations

To determine the effect of the tolerogenic peptide hCDR1 on hippocampal neurogenesis, we treated SLE-afflicted (NZBxNZW)F1 mice with hCDR1 (once a week for 10 weeks). The treatment resulted in the up-regulation of neurogenesis in the dentate gyrus and restored the NeuN immunoreactivity in brain hippocampi of the mice in association with increased gene expression of IGF-1, NGF and BDNF. Furthermore, hCDR1 treatment significantly up-regulated p-ERK and p-Akt that are suggested to be key components in mediating growth factor-induced neurogenesis. The observed effects of hCDR1 on hippocampal-neurogenesis and on associated signaling pathways suggest a potential role for hCDR1 in CNS lupus.