GDNF protection against 6-OHDA: Time dependence and requirement for protein synthesis

Cecilia M. Kearns, Wayne A. Cass, Kyle Smoot, Richard Kryscio, Don M. Gash

Research output: Contribution to journalArticlepeer-review

113 Scopus citations

Abstract

Glial cell line-derived neurotrophic factor (GDNF) injected intranigrally protects midbrain dopamine neurons against 6-hydroxydopamine (6-OHDA) toxicity. The timing between GDNF administration and exposure to 6- OHDA is critical in achieving optimal protection. When injected 6 hr before an intranigral injection of 6-OHDA, GDNF provides complete protection as measured by the number of surviving neurons in the substantia nigra of adult rats. The surviving neuronal population decreases by ~50% with 12 and 24 hr separating GDNF and 6-OHDA administrations. In controls with 6-OHDA lesions, there is <10% survival of nigral dopamine neurons. No significant increase in survival is seen with either concurrent injections of GDNF and 6-OHDA or 1 hr GDNF pretreatment. Based on HPLC measurements, striatal and midbrain dopamine levels are at least twofold higher on the lesioned side in animals receiving GDNF 6 hr before a 6-OHDA lesion compared with vehicle recipients. Protein synthesis is necessary for GDNF-induced neuroprotective effects because cycloheximide pretreatment that inhibits protein synthesis also blocks neuroprotection.

Original languageEnglish
Pages (from-to)7111-7118
Number of pages8
JournalJournal of Neuroscience
Volume17
Issue number18
DOIs
StatePublished - 1997

Funding

FundersFunder number
Institute of Neurological Disorders and Stroke National Advisory Neurological Disorders and Stroke CouncilR01NS035642
Institute of Neurological Disorders and Stroke National Advisory Neurological Disorders and Stroke Council

    Keywords

    • 6-OHDA
    • Cycloheximide
    • Dopamine neurons
    • GDNF
    • Neuroprotection
    • Substantia nigra

    ASJC Scopus subject areas

    • General Neuroscience

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