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Related Experiment Videos

Multiple astrocyte transcripts encode nigral trophic factors in rat and human

D G Schaar1, B A Sieber, A C Sherwood

  • 1Department of Neuroscience and Cell Biology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway 08854-5635.

Experimental Neurology
|December 1, 1994
PubMed
Summary
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Glial cell line-derived neurotrophic factor (GDNF) supports neuron survival. This study found GDNF RNA expression in human brain regions, suggesting it acts as a target-derived factor, with alternative transcripts also identified.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Glial cell line-derived neurotrophic factor (GDNF) is crucial for dopaminergic neuron survival.
  • Degeneration of these neurons is characteristic of Parkinson's disease.
  • Previous studies indicated GDNF's trophic support from local and target sources.

Purpose of the Study:

  • To determine the regional expression pattern of GDNF RNA in the adult human brain.
  • To identify and characterize novel GDNF-related cDNAs resulting from differential RNA processing.
  • To assess the biological significance of multiple GDNF transcript variants.

Main Methods:

  • Reverse transcription-polymerase chain reaction (RT-PCR) for GDNF mRNA expression analysis.
  • Isolation and sequencing of GDNF-related cDNAs (astrocyte-derived trophic factors - ATF).

Related Experiment Videos

  • Expression and characterization of COS-expressed GDNF and ATF-1.

    • Main Results:

    • Highest GDNF mRNA expression detected in the human caudate nucleus, with lower levels in the putamen and undetectable levels in the nigra.
    • Identification of two new GDNF-related cDNAs: human ATF-1 and ATF-2, resulting from alternative RNA processing.
    • Characterization of COS-expressed GDNF and ATF-1 demonstrated their biological actions.

    Conclusions:

    • GDNF appears to function as a target-derived neurotrophic factor in the human brain.
    • Differential RNA processing generates multiple GDNF transcript variants (ATF-1, ATF-2) in humans, conserved from rats.
    • These findings contribute to understanding GDNF's role in neuronal support and Parkinson's disease.