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Ciliary neurotrophic factor recruitment of glucagon‐like peptide‐1 mediates neurogenesis, allowing immortalization of adult murine hypothalamic neurons
Author(s) -
Belsham Denise D.,
Fick Laura J.,
Dalvi Prasad S.,
Centeno Maria-Luisa,
Chalmers Jennifer A.,
Lee Paul K. P.,
Wang Yangyang,
Drucker Daniel J.,
Koletar Margaret M.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.09-133454
Subject(s) - ciliary neurotrophic factor , neurogenesis , medicine , biology , endocrinology , hypothalamus , receptor , neurotrophic factors , microbiology and biotechnology , proglucagon , glucagon like peptide 1 , type 2 diabetes , diabetes mellitus
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. Intracere‐ broventricular 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 neurotro‐ phic factor recruitment of glucagon‐like peptide‐1 mediates neurogenesis allowing immortalization of adult murine hypothalamic neurons. FASEB J. 23, 4256–4265 (2009). www.fasebj.org