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Journal of Neuroscience, Vol 14, 1542-1554, Copyright © 1994 by Society for Neuroscience
Regulated neurotrophin receptor responsiveness during neuronal migrationand early differentiation
B Knusel, SJ Rabin, F Hefti and DR Kaplan
Division of Neurogerontology, Andrus Gerontology Center, Los Angeles.
The response of brain tissue to neurotrophins during rat development was
examined using a novel in vitro assay for Trk/neurotrophin receptor
activity. In this assay, brain tissues were exposed to neutrophins and
ligand-induced Trk tyrosine phosphorylation was measured. During the
perinatal period, Trk tyrosine phsphorylation in all brain area was induced
very similarly by the TrkB and TrkC ligands brain-derived neurotrophic
factor (BNDF), neurotrophin-3 (NT3), and neurotrophin-4/5 (NT-4/5). In the
adult brain, minimal signals were observed after treatment with these three
factors, despite the continued presence of full length and truncated TrikB
protein. In contrast, responsiveness to the TrkA ligand NGF was absent in
the ebmryo and increased during the first 2 weeks after birth in various
brain areas, particularly in striatum, basal forebrain, and hippocampus.
Our results, showing maximal responsiveness of brain tissue to BDNF, NT-3,
and NT-4/5 during early neuronal differentiation and migration, suggest
involvement of TrkB in these events. The lack of a significant response to
these neurotrophins in the adult brain indicates effective
posttranslational mechanisms that control the response of Trk family
receptors. Our findings further demonstrate that neurons of the striatum
and basal forebrain remain NGF responsive in the adult, confirming at the
molecular level results obtained earlier at the cellular level for the
basal forebrain cholinergic neurons.
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