Systemically delivered Erythropoietin transiently enhances adult hippocampal neurogenesis.
Erythropoietin is a primary regulator of erythropoiesis in the hematopoietic system. More recently erythropoietin has been shown to play a role in neurogenesis and provide neurotrophic support to injured CNS tissue. Here the effects of large systemic doses of erythropoietin on basal levels of adult hippocampal neurogenesis in mice were examined. A 7-day period of recombinant human erythropoietin (rhEPO) administration increased the number of bromodeoxyuridine [BrdU(+)] cells in the sub-granular zone (SGZ) by 30%. Analysis of cell phenotype revealed an increase in mitotically active doublecortin(+) neuronal progenitor cells and glial fibrillary acidic protein(+) SGZ radial astrocytes/stem cells but not mature S100beta(+) astrocytes. These effects appeared to be mediated, in part, by mitogen-activated protein kinase signaling and potentially regulated by suppressor of cytokine signaling-3. Hippocampal levels of phosphorylated extracellular signal-related kinase 42/44 and suppressor of cytokine signaling-3 were increased 2-6 h after a single systemic rhEPO injection. However, rhEPO had no observed effect on the long-term survival of new born cells in the SGZ, with similar numbers of BrdU(+) cells and BrdU(+)/NeuN(+) co-labeled cells after 4 weeks. Therefore, systemically delivered rhEPO transiently increased adult hippocampal neurogenesis without any apparent long-term effects.
Ransome
Mark I
MI
Neural Regeneration Laboratory, Centre for Neuroscience, University of Melbourne, Melbourne, Vic., Australia.
Turnley
Ann M
AM
Neural Regeneration Laboratory, Centre for Neuroscience, University of Melbourne, Melbourne, Vic., Australia.
D000367:Age Factors; D000818:Animals; D001973:Bromodeoxyuridine; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D004921:Erythropoietin / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007274:Injections, Intraperitoneal; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism / Q000494:pharmacology; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects* / Q000378:metabolism; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000187:drug effects / Q000378:metabolism
C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D005904:Glial Fibrillary Acidic Protein; D008869:Microtubule-Associated Proteins; D009414:Nerve Growth Factors; D009479:Neuropeptides; C491410:Socs3 protein, rat; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D004921:Erythropoietin; D001973:Bromodeoxyuridine