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Attenuation of Glutamate-induced Neuronal Swelling and Toxicity in Transgenic Mice Overexpressing Human CuZn-Superoxide Dismutase

  • P. H. Chan
  • L. Chu
  • S. F. Chen
  • E. J. Carlson
  • C. J. Epstein
Conference paper
Part of the Acta Neurochirurgica book series (NEUROCHIRURGICA, volume 51)

Summary

The role of oxygen-derived free radicals, superoxide in particular, in the pathogenesis of neuronal cell death induced by glutamate was studied using primary culture cortical neurons from transgenic mice overexpressing human CuZn-superoxide dismutase. Primary cortical neuron cultures were developed form 15-day-old fetuses of both transgenic mice and their normal littermates. Both human CuZn-superoxide dismutase and host mouse CuZn-superoxide dismutase activities in cultured neurons were identified by native gel electrophoresis followed by nitroblue tetrazolium staining. Cultured neurons grown for 10–12 days in vitro were exposed briefly to 0.5 mM glutamate for 5 minutes, followed by biochemical and morphological examinations at 2 and 4 hours. Our data have demonstrated that glutamate neurotoxicity is significantly reduced in transgenic neurons at 2 and 4 hours following exposure to glutamate, as measured by the intracellular 3-0-methyl glucose space, the efflux of lactate dehydrogenase, and by phase-contrast and bright-field trypan blue staining. These data indicate that transgenic neurons containing two-to threefold the normal amount of CnZn-superoxide dismutase activity are protected against glutamate neurotoxicity in vitro. Our results suggest that oxidative stress play an important role in glutamate-induced neuronal swelling and toxicity.

Keywords

Down Syndrome Neuronal Cell Death Trypan Blue Exclusion Glutamate Neurotoxicity Primary Cortical Neuron Culture 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • P. H. Chan
    • 1
    • 2
  • L. Chu
    • 2
  • S. F. Chen
    • 2
  • E. J. Carlson
    • 3
  • C. J. Epstein
    • 3
    • 4
  1. 1.Departments of NeurosurgeryUniversity of California, San Francisco, School of MedicineSan FranciscoUSA
  2. 2.Departments of NeurologyUniversity of California, San Francisco, School of MedicineSan FranciscoUSA
  3. 3.Departments of PediatricsUniversity of California, San Francisco, School of MedicineSan FranciscoUSA
  4. 4.Departments of Biochemistry and BiophysicsUniversity of California, San Francisco, School of MedicineSan FranciscoUSA

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