Dual-gene, dual-cell type therapy against an excitotoxic insult by bolstering neuroenergetics

Tonya M. Bliss, Miranda Ip, Elise Cheng, Masabumi Minami, Luc Pellerin, Pierre Magistretti, Robert M. Sapolsky*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)6202-6208
Number of pages7
JournalJournal of Neuroscience
Volume24
Issue number27
DOIs
StatePublished - Jul 7 2004

Keywords

  • Energy
  • Gene therapy
  • Glucose
  • Lactate
  • Neuron death
  • Neurotoxicity

ASJC Scopus subject areas

  • Neuroscience(all)

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