Neuropeptide Y Promotes Neurogenesis in Murine Subventricular Zone

¹ Neuroprotection and Neurogenesis in Brain Repair Group, Center for Neuroscience and Cell Biology, Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal.; Laboratory of Neuropsychiatry, Department of Neuroscience and Pharmacology, University of Copenhagen and Rigshospitalet University Hospital 6102, Copenhagen, Denmark.

^* To whom correspondence should be addressed. E-mail: jomalva{at}fmed.uc.pt.

	Abstract

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 48h and neuronal differentiation at 7 days in SVZ cells cultures. NPY pro-neurogenic 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 P-ERK in the nucleus, compatible with a trigger for proliferation whereas 6 hours treatment amplified P-JNK 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.