Glial cell line-derived neurotrophic factor augments midbrain dopaminergic circuits in vivo

John Hudson, Ann Charlotte Granholm, Greg A. Gerhardt, Michael A. Henry, Alex Hoffman, Paul Biddle, N. S. Leela, L. Mackerlova, Jack D. Lile, Frank Collins, Barry J. Hoffer

195 Scopus citations

Abstract

Recently, a novel glial cell line-derived neurotrophic factor (GDNF) has been identified, cloned, and shown to have potent survival- and growth-promoting activity on fetal rat midbrain dopaminergic neurons in cell culture. In this study, we document marked and long-lasting effects on adult rat midbrain dopaminergic neurons in vivo after intracranial administration. A single injection of this factor into the substantia nigra elicited a dose-dependent increase in both spontaneous and amphetamine-induced motor activity, and a decrease in food consumption, lasting 7-10 days. Using immunocytochemistry, we found sprouting of tyrosine hydroxylase-positive neurites towards the injection site, and increased tyrosine hydroxylase immunoreactivity of the ipsilateral striatum was produced by GDNF. There was also a marked and dose-dependent increase in dopamine turnover in the substantia nigra and striatum, and in ipsilateral dopamine levels in the substantia nigra. Little or no effects of GDNF were seen on norepinephrine or serotonin levels. The neurochemical changes on dopaminergic afferents persist for at least 3 weeks after a single intracranial injection of 10 μg. Taken together, these data suggest that this glial cell line-derived factor has a potent influence on adult rat dopamine neurons and may have a potentially important role as a trophic factor for these neurons.

Original languageEnglish (US)
Pages (from-to)425-432
Number of pages8
JournalBrain Research Bulletin
Volume36
Issue number5
DOIs
StatePublished - 1995

Keywords

  • Dopamine
  • GDNF
  • Parkinson's disease
  • Striatum
  • Substantia nigra
  • Trophic activity

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Hudson, J., Granholm, A. C., Gerhardt, G. A., Henry, M. A., Hoffman, A., Biddle, P., Leela, N. S., Mackerlova, L., Lile, J. D., Collins, F., & Hoffer, B. J. (1995). Glial cell line-derived neurotrophic factor augments midbrain dopaminergic circuits in vivo. Brain Research Bulletin, 36(5), 425-432. https://doi.org/10.1016/0361-9230(94)00224-O