Ciliary neurotrophic factor recruitment of glucagon‐like peptide‐1 mediates neurogenesis, allowing immortalization of adult murine hypothalamic neurons
| Autor: | Daniel J. Drucker, Margaret M. Koletar, Laura J. Fick, Jennifer A. Chalmers, Prasad S. Dalvi, Yangyang Wang, Denise D. Belsham, Maria-Luisa Centeno, Paul K. P. Lee |
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| Rok vydání: | 2009 |
| Předmět: |
Male
medicine.medical_specialty Neurogenesis Hypothalamus Ciliary neurotrophic factor Proglucagon Biochemistry Neuroprotection Cell Line Mice Glucagon-Like Peptide 1 Internal medicine Genetics medicine Animals Ciliary Neurotrophic Factor Receptor Molecular Biology Cell Proliferation Neurons biology Glucagon-like peptide-1 Mice Inbred C57BL Endocrinology Gene Expression Regulation Cell culture biology.protein Signal transduction Signal Transduction Biotechnology |
| Zdroj: | The FASEB Journal. 23:4256-4265 |
| ISSN: | 1530-6860 0892-6638 |
| Popis: | The distinct lack of cell lines derived from the adult brain is evident. Ciliary neurotrophic factor (CNTF) triggers neurogenesis in primary cul- ture 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 neuropep- tides and receptors involved in neuroendocrine func- tion. We hypothesized that proglucagon-derived pep- tides may be the mechanistic downstream effectors of CNTF due to documented neuroprotective and proliferative effects. Indeed, proglucagon gene ex- pression 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 hypo- thalamus. 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 link- ing 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 medi- ates neurogenesis allowing immortalization of adult mu- rine hypothalamic neurons. FASEB J. 23, 000-000 (2009). www.fasebj.org |
| Databáze: | OpenAIRE |
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