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

Détails

ID Serval
serval:BIB_2A4FFB6E7D1B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Dual-gene, dual-cell type therapy against an excitotoxic insult by bolstering neuroenergetics
Périodique
Journal of Neuroscience
Auteur(s)
Bliss  T. M., Ip  M., Cheng  E., Minami  M., Pellerin  L., Magistretti  P., Sapolsky  R. M.
ISSN
1529-2401 (Electronic)
Statut éditorial
Publié
Date de publication
07/2004
Volume
24
Numéro
27
Pages
6202-8
Notes
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Jul 7
Résumé
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.
Mots-clé
Animals Cell Survival/drug effects/genetics Cells, Cultured Cytoprotection/drug effects/genetics Drug Synergism Energy Metabolism/drug effects/*genetics Feasibility Studies Gene Therapy/*methods Glucose/metabolism/pharmacokinetics Glucose Transporter Type 1 Lactic Acid/metabolism/pharmacokinetics Monocarboxylic Acid Transporters/biosynthesis/genetics/pharmacology Monosaccharide Transport Proteins/biosynthesis/genetics/pharmacology Neuroglia/*drug effects/metabolism Neurons/*drug effects/*metabolism Neurotoxins/*toxicity Plasmids/genetics/pharmacology Rats Rats, Sprague-Dawley Transfection/methods Transgenes
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 13:17
Dernière modification de la notice
20/08/2019 13:09
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