title: Ciliary neurotrophic factor receptor regulation of adult forebrain neurogenesis.
abstract: Appropriately targeted manipulation of endogenous neural stem progenitor (NSP) cells may contribute to therapies for trauma, stroke, and neurodegenerative disease. A prerequisite to such therapies is a better understanding of the mechanisms regulating adult NSP cells in vivo. Indirect data suggest that endogenous ciliary neurotrophic factor (CNTF) receptor signaling may inhibit neuronal differentiation of NSP cells. We challenged subventricular zone (SVZ) cells in vivo with low concentrations of CNTF to anatomically characterize cells containing functional CNTF receptors. We found that type B "stem" cells are highly responsive, whereas type C "transit-amplifying" cells and type A neuroblasts are remarkably unresponsive, as are GFAP(+) astrocytes found outside the SVZ. CNTF was identified in a subset of type B cells that label with acute BrdU administration. Disruption of in vivo CNTF receptor signaling in SVZ NSP cells, with a "floxed" CNTF receptor α (CNTFRα) mouse line and a gene construct driving Cre recombinase (Cre) expression in NSP cells, led to increases in SVZ-associated neuroblasts and new olfactory bulb neurons, as well as a neuron subtype-specific, adult-onset increase in olfactory bulb neuron populations. Adult-onset receptor disruption in SVZ NSP cells with a recombinant adeno-associated virus (AAV-Cre) also led to increased neurogenesis. However, the maintenance of type B cell populations was apparently unaffected by the receptor disruption. Together, the data suggest that endogenous CNTF receptor signaling in type B stem cells inhibits adult neurogenesis, and further suggest that the regulation may occur in a neuron subtype-specific manner.
authors: Department of Molecular & Cellular Physiology, University of Cincinnati, Cincinnati, Ohio 45267, USA.
authors: Nancy
authors: N
authors: Lee
authors: Myra K
authors: MK
authors: Batt
authors: Brigitte A
authors: BA
authors: Cronier
authors: Michele C
authors: MC
authors: Jackson
authors: Jennifer L
authors: JL
authors: Bruno Garza
authors: Dennis S
authors: DS
authors: Trinh
authors: Carter O
authors: CO
authors: Mason
authors: Rachel P
authors: RP
authors: Spearry
authors: Shayon
authors: S
authors: Bhattacharya
authors: Rachel
authors: R
authors: Robitz
authors: Masato
authors: M
authors: Nakafuku
authors: A John
authors: AJ
authors: MacLennan
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology / Q000378:metabolism; D000818:Animals; D020934:Ciliary Neurotrophic Factor / Q000378:metabolism; D020547:Lateral Ventricles / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D009830:Olfactory Bulb / Q000166:cytology / Q000502:physiology; D016548:Prosencephalon / Q000502:physiology*; D020801:Receptor, Ciliary Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D020934:Ciliary Neurotrophic Factor; D020801:Receptor, Ciliary Neurotrophic Factor