Brain-derived neurotrophic factor (BDNF) acts through the neurotrophin receptor TrkB and promotes survival and differentiation of dopaminergic ventral mesencephalic neurons. To further evaluate the role of TrkB in the nigrostriatal pathway, we studied neurotrophin levels, dopamine metabolism, and morphology of dopaminergic neurons of the substantia nigra (SN-DA) in young adult hypomorphic trkB mice (trkB fbz/fbz), which express only approximately 25% of wild type levels of TrkB. Tyrosine hydroxylase immunostaining revealed altered morphology of SN-DA neurons in trkB fbz/fbz when compared to wild type mice, in particular a significant enlargement of nuclear size. Cell counts revealed a pronounced loss of SN-DA neurons in these mice. Measurement of monoamine levels by high performance liquid chromatography (HPLC) showed that dopamine (DA) levels in the target field (striatum) were significantly elevated in trkB fbz/fbz compared to trkB +/fbz and wild type mice (P < 0.05), without altering DA turnover. Likewise, enzyme-linked immunosorbent assay (ELISA) for neurotrophic factors measurement showed that BDNF levels were increased in the striatum (P < 0.01) and frontal cortex (P < 0.005) of trkB fbz/fbz mice, but not in the SN when compared to trkB +/fbz and wild type mice. These data suggest that elevated neurotransmitter and neurotrophic factor levels might be a compensatory mechanism following dopaminergic cell loss in the SN. Thus, TrkB-activation seems essential for the maintenance of the nigrostriatal dopaminergic system.
|Number of pages||10|
|State||Published - Dec 2004|
Bibliographical noteFunding Information:
This work was supported by EY013520, MH01245, AG06434, DAMD 17-99-1-9480, and AG15239. We thank Dr. A Ch. Granholm for valuable discussions. Alfred Moore and Rachel Singleton for technical support and Stewart Surgener for outstanding technical support for the HPLC-EC measures of DA and DA metabolites.
- Dopaminergic system
- Substantia nigra
ASJC Scopus subject areas
- Developmental Neuroscience