Ciliary neurotrophic factor receptor regulation of adult forebrain neurogenesis

Nancy Lee, Myra K. Batt, Brigitte A. Cronier, Michele C. Jackson, Jennifer L.B. Garza, Dennis S. Trinh, Carter O. Mason, Rachel P. Spearry, Shayon Bhattacharya, Rachel Robitz, Masato Nakafuku, A. John MacLennan

Research output: Contribution to journalArticle

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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 (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.

Original languageEnglish (US)
Pages (from-to)1241-1258
Number of pages18
JournalJournal of Neuroscience
Volume33
Issue number3
DOIs
StatePublished - Jan 16 2013
Externally publishedYes

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Ciliary Neurotrophic Factor Receptor
Neurogenesis
Prosencephalon
Neural Stem Cells
Lateral Ventricles
Stem Cells
Ciliary Neurotrophic Factor
Neurons
Adult Stem Cells
Olfactory Bulb
B-Lymphocyte Subsets
Dependovirus
Bromodeoxyuridine
Astrocytes
Neurodegenerative Diseases
Population
B-Lymphocytes
Stroke
Maintenance

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Lee, N., Batt, M. K., Cronier, B. A., Jackson, M. C., Garza, J. L. B., Trinh, D. S., ... John MacLennan, A. (2013). Ciliary neurotrophic factor receptor regulation of adult forebrain neurogenesis. Journal of Neuroscience, 33(3), 1241-1258. https://doi.org/10.1523/JNEUROSCI.3386-12.2013

Ciliary neurotrophic factor receptor regulation of adult forebrain neurogenesis. / Lee, Nancy; Batt, Myra K.; Cronier, Brigitte A.; Jackson, Michele C.; Garza, Jennifer L.B.; Trinh, Dennis S.; Mason, Carter O.; Spearry, Rachel P.; Bhattacharya, Shayon; Robitz, Rachel; Nakafuku, Masato; John MacLennan, A.

In: Journal of Neuroscience, Vol. 33, No. 3, 16.01.2013, p. 1241-1258.

Research output: Contribution to journalArticle

Lee, N, Batt, MK, Cronier, BA, Jackson, MC, Garza, JLB, Trinh, DS, Mason, CO, Spearry, RP, Bhattacharya, S, Robitz, R, Nakafuku, M & John MacLennan, A 2013, 'Ciliary neurotrophic factor receptor regulation of adult forebrain neurogenesis', Journal of Neuroscience, vol. 33, no. 3, pp. 1241-1258. https://doi.org/10.1523/JNEUROSCI.3386-12.2013
Lee N, Batt MK, Cronier BA, Jackson MC, Garza JLB, Trinh DS et al. Ciliary neurotrophic factor receptor regulation of adult forebrain neurogenesis. Journal of Neuroscience. 2013 Jan 16;33(3):1241-1258. https://doi.org/10.1523/JNEUROSCI.3386-12.2013
Lee, Nancy ; Batt, Myra K. ; Cronier, Brigitte A. ; Jackson, Michele C. ; Garza, Jennifer L.B. ; Trinh, Dennis S. ; Mason, Carter O. ; Spearry, Rachel P. ; Bhattacharya, Shayon ; Robitz, Rachel ; Nakafuku, Masato ; John MacLennan, A. / Ciliary neurotrophic factor receptor regulation of adult forebrain neurogenesis. In: Journal of Neuroscience. 2013 ; Vol. 33, No. 3. pp. 1241-1258.
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