Cellular targets and trophic functions of neurotrophin-3 in the developing rat hippocampus.
The expression of the neurotrophins and trk receptors in the hippocampus has directed attention toward their roles in the development and maintenance of this region. We have examined the effects of the neurotrophins NT-3, BDNF, and NGF in cultures of developing rat hippocampal cells by two criteria: rapid induction of c-fos and neurotrophic responses. The selective induction of c-fos mRNA suggests the presence of functional receptors for NT-3 and BDNF, but not NGF, in embryonic hippocampal cultures. The NT-3-responsive cells were localized in pyramidal neurons of areas CA1 through CA3 and dentate granular and hilar cells of postnatal organotypic slices, as detected by c-Fos immunocytochemistry. In addition to immediate early responses, NT-3 caused a 10-fold increase in the number of cells expressing the neuronal antigen calbindin-D28k. This increase was dose dependent, with maximal stimulation at 10 ng/ml. In contrast, BDNF elicited small but significant calbindin responses. These results indicate biological responses to NT-3 in the CNS and suggest roles for for this neurotrophin during hippocampal neurogenesis.
Collazo
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Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115.
Takahashi
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McKay
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D000818:Animals; D019208:Brain-Derived Neurotrophic Factor; D064092:Calbindin 1; D064026:Calbindins; D002478:Cells, Cultured; D005333:Fetus; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D015870:Gene Expression; D016762:Genes, fos; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D066298:In Vitro Techniques; D009414:Nerve Growth Factors / Q000494:pharmacology* / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D020933:Neurotrophin 3; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis / Q000235:genetics; D011519:Proto-Oncogenes / Q000187:drug effects*; D011712:Pyramidal Tracts / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020917:Receptor, trkA; D064030:S100 Calcium Binding Protein G / Q000032:analysis / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; C576500:Calb1 protein, rat; D064092:Calbindin 1; D064026:Calbindins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D020933:Neurotrophin 3; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D064030:S100 Calcium Binding Protein G; D016222:Fibroblast Growth Factor 2; D011505:Protein-Tyrosine Kinases; D020917:Receptor, trkA