In vivo upregulation of the blood-brain barrier GLUT1 glucose transporter by brain-derived peptides.
Glucose is the critical metabolic fluid for the brain, and the transport of this nutrient from blood to brain is limited by the blood-brain barrier (BBB) GLUT1 glucose transporter. The expression of the BBB-GLUT1 gene is augmented in brain endothelial cultured cells incubated with brain-derived trophic factors and the brain-derived peptide preparation Cerebrolysin (C1, EBEWE, Austria). The aim of the present investigation was to determine if C1 induces similar changes in the expression of the BBB-GLUT1 gene following its administration to rats in vivo. The BBB glucose transporter activity was investigated with the intracarotid artery perfusion technique using [3H]diazepam as cerebral blood flow marker. The acute or chronic administration of C1 markedly increased the brain permeability surface area of D-[14C]glucose compared to controls (D-[14C]glucose/[3H]diazepam ratio, 1.6- to 1.9-fold increase in frontal cortex, P < 0.05). Increased activity of the BBB glucose transporter was correlated with a significant rise in the abundance of the BBB-GLUT1 protein measured by both Western blot analysis and immunocytochemistry, and with a decrease in the transcript levels of this transporter. Data presented here demonstrate that the in vivo administration of Cl increases the transport of glucose from blood to brain via BBB-GLUT1 gene expression.
Boado
R J
RJ
Department of Medicine, and Brain Research Institute, UCLA School of Medicine, Los Angeles, CA 90095, USA. rboado@med1.medsch.ucla.edu
Wu
D
D
Windisch
M
M
D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D051272:Glucose Transporter Type 1; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism*; D009479:Neuropeptides / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation
D000596:Amino Acids; D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; D009479:Neuropeptides; D012333:RNA, Messenger; C495679:Slc2a1 protein, rat; C006952:cerebrolysin; D005947:Glucose