Parkinson's disease (PD) is characterized by the progressive loss of select neuronal populations, but the prodeath genes mediating the neurodegenerative processes remain to be fully elucidated. Trib3 (tribbles pseudokinase 3) is a stress-induced gene with proapoptotic activity that was previously described as highly activated at the transcriptional level in a 6-hydroxydopamine (6-OHDA) cellular model of PD. Here, we report that Trib3 immunostaining is elevated in dopaminergic neurons of the substantia nigra pars compacta (SNpc) of human PD patients. Trib3 protein is also upregulated in cellular models of PD, including neuronal PC12 cells and rat dopaminergic ventral midbrain neurons treated with 6-OHDA, 1-methyl-4-phenylpyridinium (MPP

The effects of neurotrophins during the middle and late stages of development are well known. It was previously thought that neurotrophins had no role during early development, but this is not the case and is the subject of this review article. The earliest neurotrophin receptor expressed is that for neurotrophin-3 (NT-3). TrkC is detected in the neural plate and is present in the neural tube. Initially, the distribution of TrkC is homogenous, but it becomes localized to specific regions of the neural tube as the neural tube differentiates. The receptor for brain-derived neurotrophic factor (BDNF) and neurotrophin-4/5 (NT-4/5), TrkB, is detected somewhat later than TrkC in the neural tube where it is also differentially localized. In contrast, the NGF receptor, TrkA, was not detected during early development. Both NT-3 and BDNF have been shown to have effects in vitro during early development. NT-3 caused an increase in neurite outgrowth and apoptosis in neural plate explants, and promoted differentiation of progenitors into motoneurons. BDNF increased the number of motoneurons in neural tube explants. These data suggest that NT-3 and BDNF may play a role during early development in vivo.

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The nerve growth factor (NGF) family of neurotrophins exerts effects by binding to products of the trk family of proto-oncogenes. We examined the expression of both trk and neurotrophin mRNA during the entire range of development of quail dorsal root ganglia (DRG) and sympathetic ganglia (SG) using in situ hybridization and reverse transcriptase-polymerase chain reaction (RT-PCR). TrkC mRNA was present in neurons or their precursors from the time of formation of DRG (stage 18, embryonic day 2.5 [E2.5]) and throughout development. The number of labeled cells changed, however, from a majority to a minority at later developmental stages. Expression of trkA mRNA was not detected in DRG until stage 30 (E6) by in situ hybridization, although results with RT-PCR were positive at stage 23 (E3.5). Labeling was always detected on a majority of neurons or their precursors. SG exhibited low levels of trkC mRNA during the later stages of development, whereas trkA mRNA was present from stage 34 onward in most neurons. We have also shown that NGF, neurotrophin-3 (NT-3), and brain-derived neurotrophic factor (BDNF) mRNA were present at all stages examined (stages 23 through 45 for DRG, stages 35-36 and 45 for SG). In DRG, NGF mRNA expression was limited to support cells, whereas NT-3 and BDNF mRNA were detected in both neurons and support cells. These results suggest that neurotrophins could serve a local function in developing ganglia, which can be correlated with the presence of their respective receptors.