Abstract:
: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.
journal_name
Brain Resjournal_title
Brain researchauthors
Gupta A,Ho DY,Brooke S,Franklin L,Roy M,McLaughlin J,Fink SL,Sapolsky RMdoi
10.1016/s0006-8993(01)02572-0subject
Has Abstractpub_date
2001-07-20 00:00:00pages
49-57issue
1eissn
0006-8993issn
1872-6240pii
S0006-8993(01)02572-0journal_volume
908pub_type
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