HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Data Buy All Versions of this Article: fj.09-133454v1 23/12/4256    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Belsham, D. D. Articles by Koletar, M. M. PubMed PubMed Citation Articles by Belsham, D. D. Articles by Koletar, M. M.

Ciliary neurotrophic factor recruitment of glucagon-like peptide-1 mediates neurogenesis, allowing immortalization of adult murine hypothalamic neurons

Denise D. Belsham^*,,,||,1, Laura J. Fick^*, Prasad S. Dalvi^*, Maria-Luisa Centeno^*, Jennifer A. Chalmers^*, Paul K. P. Lee^*, Yangyang Wang^*, Daniel J. Drucker^,¶ and Margaret M. Koletar^*,

^* Department of Physiology,

Department of Obstetrics and Gynaecology,

Department of Medicine, and

Department of Psychology, University of Toronto, Toronto, Ontario, Canada;

^|| Division of Cellular and Molecular Biology, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada; and

^¶ Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada

¹ Correspondence: Department of Physiology, University of Toronto, Medical Sciences Bldg. 3247A, 1 King’s College Cir., Toronto, ON, Canada M5S 1A8. E-mail: d.belsham{at}utoronto.ca

The distinct lack of cell lines derived from the adult brain is evident. Ciliary neurotrophic factor (CNTF) triggers neurogenesis in primary culture from adult mouse hypothalamus, as detected by bromodeoxyuridine and Ki67 immunostaining. Using SV-40 T-antigen, we immortalized dividing neurons and generated clonal cell lines expressing neuropeptides and receptors involved in neuroendocrine function. We hypothesized that proglucagon-derived peptides may be the mechanistic downstream effectors of CNTF due to documented neuroprotective and proliferative effects. Indeed, proglucagon gene expression was induced by CNTF, and exposure of primary cells to glucagon-like peptide-1 receptor (GLP-1) agonist, exendin-4, induced cell proliferation. Intracerebroventricular injection of CNTF into adult mice caused increased expression of proglucagon peptide in the hypothalamus. Using a specific GLP-1-receptor antagonist, we found that neurogenesis was significantly attenuated and primary culture from GLP-1-receptor-knockout mice lacked CNTF-mediated neuronal proliferation, thus linking the induction of neurogenesis in the hypothalamus to GLP-1-receptor signaling.—Belsham, D. D., Fick, L. J., Dalvi, P. S., Centeno, M.-L., Chalmers, J. A., Lee, P. K. P., Wang, Y., Drucker, D. J., Koletar, M. M. Ciliary neurotrophic factor recruitment of glucagon-like peptide-1 mediates neurogenesis allowing immortalization of adult murine hypothalamic neurons.

Key Words: adult neuronal cell lines • neuroendocrinology • proglucagon • signal transduction