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 10weeks). 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.
Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.
Alona
A
Telerman
Smadar
S
Lapter
Amir
A
Sharabi
Heidy
H
Zinger
Edna
E
Mozes
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015153:Blotting, Western; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D020945:Lupus Vasculitis, Central Nervous System / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009414:Nerve Growth Factors / Q000187:drug effects; D055495:Neurogenesis / Q000187:drug effects*; D010446:Peptide Fragments / Q000627:therapeutic use*; D011494:Protein Kinases / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects
D000911:Antibodies, Monoclonal; D009414:Nerve Growth Factors; D010446:Peptide Fragments; C516151:edratide; D011494:Protein Kinases