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

• Published in: Brain research 2001-07, Vol.908 (1), p.49-57
• Main Authors: Gupta, Anurag, Ho, Dora Y, Brooke, Sheila, Franklin, Laura, Roy, Madhuri, McLaughlin, John, Fink, Sheri L, Sapolsky, Robert M
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate - metabolism; Adenoviridae - metabolism; Adenovirus; Animals; Biochemistry and metabolism; Biological and medical sciences; Brain Injuries - metabolism; Brain Injuries - physiopathology; Brain Injuries - therapy; Calcium; Cells, Cultured - cytology; Cells, Cultured - drug effects; Cells, Cultured - metabolism; Central nervous system; Deoxyglucose - pharmacokinetics; Excitatory Amino Acids - metabolism; Excitotoxicity; Fetus; Fundamental and applied biological sciences. Psychology; Gene therapy; Genetic Therapy - methods; Genetic Vectors - metabolism; Glucose - metabolism; Glucose transporter; Glucose Transporter Type 1; Glutamate; Hippocampus - cytology; Hippocampus - drug effects; Hippocampus - metabolism; Monosaccharide Transport Proteins - genetics; Monosaccharide Transport Proteins - metabolism; Necrosis; Nerve Degeneration - metabolism; Nerve Degeneration - physiopathology; Neuroglia - cytology; Neuroglia - drug effects; Neuroglia - metabolism; Neurons - cytology; Neurons - drug effects; Neurons - metabolism; Neuroprotective Agents - metabolism; Oxygen radical; Rats; Rats, Sprague-Dawley; Spectrin; Vertebrates: nervous system and sense organs
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(01)02572-0

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.