Dora Ho

Publication Details

  • Sparing of neuronal function postseizure with gene therapy PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA MCLAUGHLIN, J., Roozendaal, B., Dumas, T., Gupta, A., Ajilore, O., Hsieh, J., Ho, D., Lawrence, M., McGaugh, J. L., Sapolsky, R. 2000; 97 (23): 12804-12809

    Abstract:

    Numerous studies have demonstrated that gene therapy interventions can protect neurons from death after neurological insults. In nearly all such studies, however, "protection" consists of reduced neurotoxicity, with no demonstrated preservation of neuronal function. We used a herpes simplex virus-1 system to overexpress either the Glut-1 glucose transporter (GT) (to buffer energetics), or the apoptosis inhibitor Bcl-2. Both decreased hippocampal neuron loss to similar extents during excitotoxic insults in vitro and in vivo. However, the mediating mechanisms and consequences of the two interventions differed. GT overexpression attenuated early, energy-dependent facets of cell death, blocking oxygen radical accumulation. Bcl-2 expression, in contrast, blocked components of death downstream from the energetic and oxidative facets. Most importantly, GT- but not Bcl-2-mediated protection preserved hippocampal function as assessed spatial maze performance. Thus, gene therapeutic sparing of neurons from insult-induced death does not necessarily translate into sparing of function.

    View details for Web of Science ID 000165225800082

    View details for PubMedID 11058147

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