Corticotropin-releasing factor and urocortin differentially modulate rat Purkinje cell dendritic outgrowth and differentiation in vitro.
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.
Swinny
J D
JD
Laboratory for Cell Biology and Electron Microscopy, Graduate School of Behavioural and Cognitive Neurosciences, University of Groningen, The Netherlands.
Metzger
F
F
IJkema-Paassen
J
J
Gounko
N V
NV
Gramsbergen
A
A
van der Want
J J L
JJ
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D064026:Calbindins; D002227:Carbazoles / Q000494:pharmacology; D002452:Cell Count / Q000379:methods; D002454:Cell Differentiation / Q000187:drug effects*; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D003712:Dendrites / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D016014:Linear Models; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011689:Purkinje Cells / Q000166:cytology* / Q000187:drug effects; D011743:Pyrimidines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D013997:Time Factors; D054832:Urocortins
D064026:Calbindins; D002227:Carbazoles; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007211:Indoles; D018696:Neuroprotective Agents; D011743:Pyrimidines; D011758:Pyrroles; D064030:S100 Calcium Binding Protein G; D054832:Urocortins; C103016:antalarmin; C057416:KT 5720; D003346:Corticotropin-Releasing Hormone; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one