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Systemically delivered Erythropoietin transiently enhances adult hippocampal neurogenesis
Author(s) -
Ransome Mark I.,
Turnley Ann M.
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.04684.x
Subject(s) - neurogenesis , erythropoietin , subgranular zone , hippocampal formation , microbiology and biotechnology , gliogenesis , biology , neun , progenitor cell , glial fibrillary acidic protein , neural stem cell , endocrinology , stem cell , medicine , immunology , subventricular zone , immunohistochemistry
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 S100β(+) 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.