Alterations in blood-brain barrier glucose transport in SIV-infected macaques.
The neurological manifestations of HIV infection may be in part due to alterations in the blood-brain barrier. These may be caused by structural changes in the barrier or may consist of subtle metabolic or biochemical disturbances in barrier function. In the CNS, the family of glucose transporter proteins plays a key role in controlling movement of glucose across cell membranes. The 55 kDa isoform of glucose transporter 1 (GLUT1) regulates import of glucose from blood to brain across the endothelial cells of the blood-brain barrier (BBB), whereas the 45 kDa form of GLUT1 predominantly regulates nonvascular glial glucose uptake. In this study, expression of 55 and 45 kDa forms of GLUT1 in different regions of the brain from 18 SIV-infected macaques was measured by quantitative immunoblot and then compared with the severity of SIV encephalitis to determine whether neurologic disease is related to altered glucose metabolism at the BBB and in brain parenchyma. An inverse relationship was found between severity of SIV encephalitis and expression of the endothelial 55 kDa isoform of GLUT1 at the BBB in cortical grey matter, caudate nucleus, and cerebellum. A similar relationship also was found for the glial 45 kDa GLUT1 isoform in cortical grey matter. In addition, a significant increase in 55 kDa GLUT1 expression was found in caudate nucleus during the early stages of infection. In the brains of macaques with moderate to severe encephalitis, 55 kDa GLUT1 expression had declined to pre-infection levels. These GLUT1 alterations at the BBB and in glial cells may reflect severe disturbances in the CNS microenvironment that contribute to CNS dysfunction.
Mankowski
J L
JL
Division of Comparative Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, MD 21205, USA.
Queen
S E
SE
Kirstein
L M
LM
Spelman
J P
JP
Laterra
J
J
Simpson
I A
IA
Adams
R J
RJ
Clements
J E
JE
Zink
M C
MC
D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology*; D001921:Brain / Q000098:blood supply / Q000378:metabolism*; D002421:Caudate Nucleus / Q000378:metabolism / Q000473:pathology; D002531:Cerebellum / Q000378:metabolism / Q000473:pathology; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D018792:Encephalitis, Viral / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D004730:Endothelium, Vascular / Q000378:metabolism; D051272:Glucose Transporter Type 1; D006179:Gyrus Cinguli / Q000378:metabolism / Q000473:pathology; D015151:Immunoblotting; D008254:Macaca nemestrina; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D013997:Time Factors
D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins