Alterations in blood-brain barrier glucose transport in SIV-infected macaques

The neurological manifestations of HIV infection may be in part due to alte rations in the blood-brain barrier. These may be caused hy structural chang es in the barrier or may consist of subtle metabolic or biochemical disturb ances in barrier function. In the CNS, the family of glucose transporter pr oteins plays a key role in controlling movement of glucose across cell memb ranes. The 55 kDa isoform of glucose transporter 1 (GLUT1) regulates import of glucose from blood to brain across the endothelial cells of the blood-b rain barrier (BBB), whereas the 45 kDa form of GLUT1 predominantly regulate s 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 m acaques was measured by quantitative immunoblot and then compared with the severity of SIV encephalitis to determine whether neurologic disease is rel ated to altered glucose metabolism at the BBB and in brain parenchyma. An i nverse relationship was found between severity of SIV encephalitis and expr ession of the endothelial 55 kDa isoform of GLUT1 at the BBB in cortical gr ey matter, caudate nucleus, and cerebellum A similar relationship also was found for the glial 45 kDa GLUT1 isoform in cortical grey matter. In additi on, a significant increase in 55 kDa GLUT1 expression was found in caudate nucleus during the early stages of infection. In the brains of macaques wit h 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 contribut e to CNS dysfunction.