Bone morphogenetic protein-2, but not bone morphogenetic protein-7, promotes dendritic growth and calbindin phenotype in cultured rat striatal neurons.
Bone morphogenetic proteins are members of the transforming growth factor-beta superfamily. They are widely expressed in the mammalian nervous system, where they exert trophic effects on several neuronal populations. We studied the neurotrophic activity of bone morphogenetic protein-2 and bone morphogenetic protein-7 (also called osteogenic protein-1) on cultured striatal cells, previously shown to express bone morphogenetic protein ligands and receptors. Our results indicate that only bone morphogenetic protein-2 promoted the differentiation of GABAergic neurons, especially of the calbindin-positive subpopulation, the subset of projecting striatal neurons that degenerates in Huntington's disease. Bone morphogenetic protein-2 increased the area, perimeter and degree of arborization of GABAergic neurons, promoting calbindin phenotype without altering proliferation or apoptosis. In contrast, neither bone morphogenetic protein-2 nor -7 affected striatal cholinergic interneurons. However, they both increased the number of glial fibrillary acidic protein-positive cells. Suppression of glial proliferation with 5-fluorodeoxyuridine did not abolish bone morphogenetic protein-2 effects on the differentiation of striatal neurons, ruling out an indirect mechanism through astrocytes. In conclusion, our results show that bone morphogenetic protein-2 promotes the differentiation of cultured GABAergic striatal neurons, suggesting that bone morphogenetic proteins are involved in the development of the striatum.
Gratacòs
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Departament de Biologia Cel.lular i Anatomia Patològica, Facultat de Medicina, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Universitat de Barcelona, Casanova 143, E-08036, Barcelona, Spain.
Checa
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N
Alberch
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J
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D064026:Calbindins; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D048429:Cell Size / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003712:Dendrites / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005333:Fetus; D005467:Floxuridine / Q000494:pharmacology; D007150:Immunohistochemistry; D017072:Neostriatum / Q000166:cytology / Q000187:drug effects* / Q000196:embryology; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D064030:S100 Calcium Binding Protein G / Q000187:drug effects* / Q000378:metabolism; D016212:Transforming Growth Factor beta; D014529:Uridine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000493:pharmacokinetics
D000964:Antimetabolites, Antineoplastic; C525720:Bmp2 protein, rat; C525821:Bmp7 protein, rat; D055396:Bone Morphogenetic Protein 2; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D064026:Calbindins; D064030:S100 Calcium Binding Protein G; D016212:Transforming Growth Factor beta; D005467:Floxuridine; D005680:gamma-Aminobutyric Acid; D002795:Choline O-Acetyltransferase; D014529:Uridine