Ligand Brain-derived Neurotrophic Factor Research Articles

Up-regulation of trkB mRNA expression in the rat striatum after seizures

The present study investigates the expression of a tyrosine kinase receptor ( trkB), its specific ligands brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4) mRNAs in the striatum after seizures. The result showed an increase of trkB mRNA expression, both with and without tyrosine kinase domain, in the caudate-putamen and nucleus accumbens, but not in the globus pallidus. This increase peaked 3 h after treatment, and returned to normal levels by 12 h. The BDNF and NT-4 mRNAs showed no change at any time. In conclusion, the widespread and massive trkB mRNA induction after abnormal neuronal activity suggests local trophic support for this receptor, and a potential role in basal ganglia diseases involving non-dopaminergic components.

Regulated neurotrophin receptor responsiveness during neuronal migrationand early differentiation

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.