Progressive hippocampal loss of immunoreactive GLUT3, the neuron-specific glucose transporter, after global forebrain ischemia in the rat.
Brain damage after global forebrain ischemia is worsened by prior hyperglycemia and ameliorated by antecedent hypoglycemia. To assess whether GLUT3, the neuron specific glucose transporter and its mRNA, are affected by cerebral ischemia, we investigated the hippocampal pattern of GLUT3 immunoreactivity and GLUT3 gene expression 1, 4 and 7 days after global forebrain ischemia in a rat 2-vessel occlusion model. We used a newly generated, specific, C-terminally directed polyclonal antiserum against GLUT3 to stain coronal frozen sections. Thionin staining and the microglial marker, OX42, indicated the extent of ischemic damage in hippocampus and correlated with GLUT3 loss. One day after ischemia, no significant change in hippocampal GLUT3 immunoreactivity was observed; by 4 days however, there was consistent and pronounced loss; and at 7 days the loss of GLUT3 staining was maximal. The greatest loss of GLUT3 staining was in the CA1 region, especially the strata oriens and radiatum of Ammon's horn. By contrast, GLUT3 staining was undiminished in the stratum lacunosum moleculare, in the mossy fibers of the lateral aspect of CA3 and in all but the inner-most portion of the molecular layer of the dentate gyrus, immediately adjacent to the granule cells. GLUT3 mRNA levels were not significantly altered at 24 hours and significantly declined at 4 and 7 days after ischemia in the CA1 pyramidal layer. These data are consistent with the pattern of neuronal loss and microglial activation in hippocampus. Loss of GLUT3 may affect the availability of glucose, and possibly the viability of ischemically damaged neurons.
McCall
A L
AL
Department of Cell Biology and Anatomy, Oregon Health Sciences University, Portland 97207, USA.
Moholt-Siebert
M
M
VanBueren
A
A
Cherry
N J
NJ
Lessov
N
N
Tiffany
N
N
Thompson
M
M
Downes
H
H
Woodward
W R
WR
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D004195:Disease Models, Animal; D015870:Gene Expression; D051274:Glucose Transporter Type 3; D006624:Hippocampus / Q000098:blood supply / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D016548:Prosencephalon; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
D051274:Glucose Transporter Type 3; D009004:Monosaccharide Transport Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C495690:Slc2a3 protein, rat