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 successful attempts to use gene therapy approaches to protect neurons from such necrotic injury. In many such studies, however, it is not clear what sequence of cellular events connects the overexpression of the transgene with the enhanced survival. We do so, exploring the effects of overexpressing the Glut-1 glucose transporter with an adenoviral vector in hippocampal cultures challenged with the excitotoxin kainic acid (KA). Such overexpression enhanced glucose transport, attenuated the decline in ATP concentrations, decreased the release of excitatory amino acid neurotransmitters, and decreased the total free cytosolic calcium load. Commensurate with these salutary effects, 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.
Gupta
A
A
Department of Biological Sciences, Stanford University, 95406, Stanford, CA, USA.
Ho
D Y
DY
Brooke
S
S
Franklin
L
L
Roy
M
M
McLaughlin
J
J
Fink
S L
SL
Sapolsky
R M
RM
D000255:Adenosine Triphosphate / Q000378:metabolism; D000256:Adenoviridae / Q000378:metabolism*; D000818:Animals; D001930:Brain Injuries / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D003847:Deoxyglucose / Q000493:pharmacokinetics; D018846:Excitatory Amino Acids / Q000378:metabolism; D005333:Fetus; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D051272:Glucose Transporter Type 1; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000235:genetics* / Q000378:metabolism; D009336:Necrosis; D009410:Nerve Degeneration / Q000378:metabolism* / Q000503:physiopathology; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018846:Excitatory Amino Acids; D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; D018696:Neuroprotective Agents; C495679:Slc2a1 protein, rat; D000255:Adenosine Triphosphate; D003847:Deoxyglucose; D005947:Glucose