The TrkB-Positive Dopaminergic Neurons are Less Sensitive to MPTP Insult in the Substantia Nigra of Adult C57/BL Mice |
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Authors: | Yin-Xiu Ding Yi Xia Xi-Ying Jiao Li Duan Jun Yu Xi Wang Liang-Wei Chen |
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Institution: | (1) Institute of Neurosciences, The Fourth Military Medical University, Xi’an, 710032, People’s Republic of China;(2) Department of Human Anatomy, Ningxia Medical University, Yinchuan, 710006, People’s Republic of China;(3) Center of Teaching Experiment, The Fourth Military Medical University, Xi’an, 710032, People’s Republic of China; |
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Abstract: | Tyrosine kinase receptors TrkB and TrkC mediate neuroprotective effects of the brain-derived neurotrophic factor (BDNF) and
neurotrophins in the dopaminergic nigro-striatal system, but it is obscure about their responses or expression changes in
the injured substantia nigra under Parkinson’s disease. In present study, immunofluorescence, Fluoro-Jade staining and laser
scanning confocal microscopy were applied to investigate distribution and changes of TrkB and TrkC in the dopamine neurons
of the substantia nigra by comparison of control and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model. It revealed
that TrkB and TrkC-immunoreactivities were substantially localized in cytoplasm and cell membrane of the substantia nigra
neurons of control adults. While neurons double-labeled with tyrosine hydroxylase (TH)/TrkB, or TH/TrkC were distributed in
a large numbers in the substantia nigra of controls, they apparently went down at 36.2–65.7% of normal level, respectively
following MPTP insult. In MPTP model, cell apoptosis or degeneration of nigral neurons were confirmed by caspase-3 and Fluoro-Jade
staining. More interestingly, TH/TrkB-positive neurons survived more in cell numbers in comparison with that of TH/TrkC-positive
ones in the MPTP model. This study has indicated that TrkB-containing dopamine neurons are less sensitive in the substantia
nigra of MPTP mouse model, suggesting that specific organization of Trks may be involved in neuronal vulnerability to MPTP
insult, and BDNF-TrkB signaling may play more important role in protecting dopamine neurons and exhibit therapeutic potential
for Parkinson’s disease. |
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