Neuroprotective effects of an adenoviral vector expressing the glucose transporter: a detailed description of the mediating cellular events

Considerable knowledge exists concerning the events mediating neuron death following a necrotic insult; prompted by this, there have now been successf ul attempts to use gene therapy approaches to protect neurons from such nec rotic injury. In many such studies, however, it is not clear what sequence of cellular events connects the overexpression of the transgene with the en hanced survival. We do so, exploring the effects of overexpressing the Glut -1 glucose transporter with an adenoviral vector in hippocampal cultures ch allenged with the excitotoxin kainic acid (KA). Such overexpression enhance d glucose transport, attenuated the decline in ATP concentrations, decrease d the release of excitatory amino acid neurotransmitters, and decreased the total free cytosolic calcium load. Commensurate with these salutary effect s, neuronal survival was enhanced with this gene therapy intervention. Thus , the neuroprotective effects of this particular gene therapy occurs within the known framework of the mechanisms of necrotic neuronal injury. (C) 200 1 Elsevier Science B.V. All rights reserved.