Corticotropin-releasing factor and urocortin differentially modulate rat Purkinje cell dendritic outgrowth and differentiation in vitro
Autor: | Albert Gramsbergen, Natalia V. Gounko, J. J. L. van der Want, J. IJkema-Paassen, Friedrich Metzger, Jerome D. Swinny |
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Rok vydání: | 2004 |
Předmět: |
Calbindins
Cerebellum Indoles Time Factors Corticotropin-Releasing Hormone Cellular differentiation Purkinje cell Cell Count Hippocampus DESENSITIZATION stress Purkinje Cells POTENTIAL MECHANISM PKA Drug Interactions Enzyme Inhibitors Urocortins Urocortin trophic General Neuroscience LOCALIZATION Cell Differentiation FACTOR RECEPTORS Immunohistochemistry Neuroprotective Agents medicine.anatomical_structure Signal transduction hormones hormone substitutes and hormone antagonists endocrine system medicine.medical_specialty cerebellum Carbazoles In Vitro Techniques Biology SIGNALING PATHWAYS S100 Calcium Binding Protein G Internal medicine medicine Animals Humans Pyrroles PROTEIN-KINASE-C Protein kinase A Protein kinase C MOUSE CEREBELLUM Flavonoids Analysis of Variance Dose-Response Relationship Drug HIPPOCAMPAL-NEURONS CENTRAL-NERVOUS-SYSTEM Dendrites MAPK Rats Pyrimidines Endocrinology Animals Newborn Linear Models CEREBELLAR SLICE CULTURES |
Zdroj: | European Journal of Neuroscience, 19(7), 1749-1758. Blackwell Publishing |
ISSN: | 1460-9568 0953-816X |
DOI: | 10.1111/j.1460-9568.2004.03279.x |
Popis: | The precise outgrowth and arborization of dendrites is crucial for their function as integrators of signals relayed from axons and, hence, the functioning of the brain. Proper dendritic differentiation is particularly resonant for Purkinje cells as the intrinsic activity of this cell-type is governed by functionally distinct regions of its dendritic tree. Activity-dependent mechanisms, driven by electrical signaling and trophic factors, account for the most active period of dendritogenesis. An as yet unexplored trophic modulator of Purkinje cell dendritic development is corticotropin-releasing factor (CRF) and family member, urocortin, both of which are localized in climbing fibers. Here, we use rat organotypic cerebellar slice cultures to investigate the roles of CRF and urocortin on Purkinje cell dendritic development. Intermittent exposure (12 h per day for 10 days in vitro) of CRF and urocortin induced significantly more dendritic outgrowth (45% and 70%, respectively) and elongation (25% and 15%, respectively) compared with untreated cells. Conversely, constant exposure to CRF and urocortin significantly inhibited dendritic outgrowth. The trophic effects of CRF and urocortin are mediated by the protein kinase A and mitogen-activating protein kinase pathways. The study shows unequivocally that CRF and urocortin are potent regulators of dendritic development. However, their stimulatory or inhibitory effects are dependent upon the degree of expression of these peptides. Furthermore, the effects of CRF and urocortin on neuronal differentiation and re-modeling may provide a cellular basis for pathologies such as major depression, which show perturbations in the expression of these stress peptides. |
Databáze: | OpenAIRE |
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