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TISSUE-SPECIFIC STEM CELLS |
aNeuroprotection and Neurogenesis in Brain Repair Group, Center for Neuroscience and Cell Biology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal;
bLaboratory of Neuropsychiatry, Department of Neuroscience and Pharmacology, University of Copenhagen and Rigshospitalet University Hospital, Copenhagen, Denmark
Key Words. Subventricular zone • Calcium imaging • Neuronal differentiation • Functional binding • Neurogenesis • Neuropeptide Y
Correspondence: João O. Malva, Ph.D., Center for Neuroscience and Cell Biology, Institute of Biochemistry, Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal. Telephone: 351-239-112254; Fax: 351-239-822776; e-mail: jomalva{at}fmed.uc.pt
Received January 17, 2008;
accepted for publication March 24, 2008.
First published online in STEM CELLS EXPRESS April 3, 2008.
Stem cells of the subventricular zone (SVZ) represent a reliable source of neurons for cell replacement. Neuropeptide Y (NPY) promotes neurogenesis in the hippocampal subgranular layer and the olfactory epithelium and may be useful for the stimulation of SVZ dynamic in brain repair purposes. We describe that NPY promotes SVZ neurogenesis. NPY (1 µM) treatments increased proliferation at 48 hours and neuronal differentiation at 7 days in SVZ cell cultures. NPY proneurogenic properties are mediated via the Y1 receptor. Accordingly, Y1 receptor is a major active NPY receptor in the mouse SVZ, as shown by functional autoradiography. Moreover, short exposure to NPY increased immunoreactivity for the phosphorylated form of extracellular signal-regulated kinase 1/2 in the nucleus, compatible with a trigger for proliferation, whereas 6 hours of treatment amplified the phosphorylated form of c-Jun-NH2-terminal kinase signal in growing axons, consistent with axonogenesis. NPY, as a promoter of SVZ neurogenesis, is a crucial factor for future development of cell-based brain therapy.
Disclosure of potential conflicts of interest is found at the end of this article.
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