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Mesencephalic dopaminergic neurons protected by GDNF from axotomy-induced degeneration in the adult brain

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Abstract

GLIAL-CELL-LINE-DERIVED neurotrophic factor (GDNF) promotes survival of embryonic dopaminergic neurons in culture1, and its expression pattern suggests a role as a transient target-derived trophic factor for dopaminergic neurons of the substantia nigra2–4. These neurons participate in the control of motor activity, emotional status and cognition5, and they degenerate in Parkinson's disease for unknown reasons. To test whether GDNF has a trophic effect on dopaminergic neurons in the adult brain, we used a rat model in which these neurons are induced to degenerate by transecting their axons within the medial forebrain bundle6. We report here that axotomy resulted in loss of half the tyrosine hydroxylase-expressing neurons in the substantia nigra. This loss was largely prevented by repeated injections of GDNF adjacent to the substantia nigra. Our findings suggest that GDNF or related molecules may be useful for the treatment of Parkinson's disease.

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Author notes

  1. Tajrena Alexi: Andrus Gerontology Center, University of Southern California, Los Angeles, California 90089, USA

Authors and Affiliations

  1. Departments of Neuroscience, Protein Chemistry and Cell Genetics, Genentech Inc., South San Francisco, California, 94080, USA

    Klaus D. Beck, Janet Valverde, Tajrena Alexi, Kris Poulsen, Barbara Moffat, Richard A. Vandlen, Arnon Rosenthal & Franz Hefti

Authors
  1. Klaus D. Beck
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  2. Janet Valverde
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  3. Tajrena Alexi
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  4. Kris Poulsen
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  5. Barbara Moffat
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  6. Richard A. Vandlen
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  7. Arnon Rosenthal
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  8. Franz Hefti
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Beck, K., Valverde, J., Alexi, T. et al. Mesencephalic dopaminergic neurons protected by GDNF from axotomy-induced degeneration in the adult brain. Nature 373, 339–341 (1995). https://doi.org/10.1038/373339a0

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  • DOI: https://doi.org/10.1038/373339a0

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