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The TrkB-Positive Dopaminergic Neurons are Less Sensitive to MPTP Insult in the Substantia Nigra of Adult C57/BL Mice

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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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Abbreviations

BDNF:

Brain-derived neurotrophic factor

GDNF:

Glial-derived neurotrophic factor

MPTP:

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

NGF:

Nerve growth factor

NT-3:

Neurotrophins-3

PB:

Phosphate buffer

PD:

Parkinson’s disease

TH:

Tyrosine hydroxylase

Trks:

Tyrosine kinase receptors

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Acknowledgments

This work was supported by grants from National Natural Science Foundation (81071609, 30970862 and 30772279) and Basic Research Program of China (2011CB504103).

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Authors and Affiliations

  1. Institute of Neurosciences, The Fourth Military Medical University, Xi’an, 710032, People’s Republic of China

    Yin-Xiu Ding, Yi Xia, Xi-Ying Jiao, Li Duan, Xi Wang & Liang-Wei Chen

  2. Department of Human Anatomy, Ningxia Medical University, Yinchuan, 710006, People’s Republic of China

    Yin-Xiu Ding

  3. Center of Teaching Experiment, The Fourth Military Medical University, Xi’an, 710032, People’s Republic of China

    Jun Yu

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  1. Yin-Xiu Ding
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Ding, YX., Xia, Y., Jiao, XY. et al. The TrkB-Positive Dopaminergic Neurons are Less Sensitive to MPTP Insult in the Substantia Nigra of Adult C57/BL Mice. Neurochem Res 36, 1759–1766 (2011). https://doi.org/10.1007/s11064-011-0491-5

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