Journal
JOURNAL OF NEUROSCIENCE
Volume 24, Issue 27, Pages 6202-6208Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.0805-04.2004
Keywords
lactate; glucose; gene therapy; neuron death; energy; neurotoxicity
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Funding
- NINDS NIH HHS [P01 NS037520, 2P01 NS037520-02] Funding Source: Medline
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Increasing evidence suggests that glutamate activates the generation of lactate from glucose in astrocytes; this lactate is shuttled to neurons that use it as a preferential energy source. We explore this multicellular lactate shuttle with a novel dual-cell, dual-gene therapy approach and determine the neuroprotective potential of enhancing this shuttle. Viral vector-driven overexpression of a glucose transporter in glia enhanced glucose uptake, lactate efflux, and the glial capacity to protect neurons from excitotoxicity. In parallel, overexpression of a lactate transporter in neurons enhanced lactate uptake and neuronal resistance to excitotoxicity. Finally, overexpression of both transgenes in the respective cell types provided more protection than either therapy alone, demonstrating that a dual-cell, dual-gene therapy approach gives greater neuroprotection than the conventional single-cell, single-gene strategy.
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