Neuroprotective effects of GDNF against 6-OHDA in young and aged rats

Cecilia M. Fox, Don M. Gash, M. Kyle Smoot, Wayne A. Cass

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

In young adult rats, glial cell line-derived neurotrophic factor (GDNF) can completely protect against 6-hydroxydopamine-induced loss of nigral dopamine neurons when administered 6 h prior to the 6-hydroxydopamine. The present study was undertaken to determine if GDNF would provide similar protective effects in aged rats. Male, Fischer 344×Brown Norway hybrid rats of 3, 18 and 24 months of age were given an intranigral injection of GDNF or vehicle followed 6 h later with an intranigral injection of 6-hydroxydopamine. Nigral dopamine neuron cell survival, and striatal and nigral dopamine and DOPAC levels, were evaluated 2 weeks after the lesions. In vehicle treated animals cell survival on the lesioned side ranged from 15 to 27%. GDNF promoted significant cell survival in the nigra of all three age groups; however, the percent survival was lowest in the 24-month-old animals (85% at 3 months, 75% at 18 months, 56% at 24 months). Similarly, dopamine levels in the striatum and substantia nigra on the lesioned side remained significantly greater in the GDNF treated animals compared to the vehicle treated animals. As with the cell survival experiment, the protective effects of GDNF on dopamine levels were less in the 24-month-old animals. GDNF pretreatment also protected against 6-hydroxydopamine-induced reductions in striatal DOPAC levels in all age groups. Overall, these results indicate that GDNF can protect nigrostriatal dopamine neurons against the effects of 6-hydroxydopamine in aged as well as young adult rats. However, the extent of protection is less in the aged (24-month-old) animals.

Original languageEnglish
Pages (from-to)56-63
Number of pages8
JournalBrain Research
Volume896
Issue number1-2
DOIs
StatePublished - Mar 30 2001

Bibliographical note

Funding Information:
This work was supported in part by USPHS grant AG13324. We thank Amgen, Inc. (Thousand Oaks, CA) for the provision of GDNF.

Keywords

  • Dopamine
  • Glial cell line-derived neurotrophic factor (GDNF)
  • Neuroprotection
  • Striatum
  • Substantia nigra
  • Tyrosine hydroxylase

ASJC Scopus subject areas

  • Neuroscience (all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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