Glucose transport is reduced in the blood-brain barrier of aged rats.
To determine the biochemical basis of decreased brain uptake of glucose with age, the brain influx of 3-O-methylglucose (3-O-MG) was measured in male Fischer 344 rats at various ages using the arterial injection-tissue sampling technique of Oldendorf. The Vmax of 3-O-MG transport in the 24-month-old rats (0.22 +/- 0.14 mumol/min/g) was significantly lower than that in 3-month-old rats (0.88 +/- 0.18 mumol/min/g) (P less than 0.05). The Km of transport in aged rats (10.1 +/- 4.8 mM) was not different from that in young rats (8.1 +/- 2.5 mM). The cytochalasin B binding sites in cerebral microvessels isolated from aged rats (13.9 +/- 0.9 pmol/mg) compared to the binding sites in cerebral microvessels of young rats (21.9 +/- 1.4 pmol/mg) were significantly reduced (P less than 0.001). However, the immunoreactive mass of glucose transporter of cerebral microvessels was not altered with age. The enrichment of capillary preparations with gamma-glutamyl transpeptidase activity, a marker of endothelial cells, was not altered in aged rats, suggesting that the reduced blood-brain barrier transport of glucose is due to specific reduction in glucose binding sites of the transporter rather than secondary to a non-specific age-related effect of endothelial cell drop-out.
Mooradian
A D
AD
Tucson VA Medical Center, University of Arizona College of Medicine 85719.
Morin
A M
AM
Cipp
L J
LJ
Haspel
H C
HC
D019325:3-O-Methylglucose; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D001786:Blood Glucose / Q000378:metabolism*; D001808:Blood Vessels / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000502:physiology*; D002560:Cerebrovascular Circulation; D003571:Cytochalasin B / Q000378:metabolism; D004586:Electrophoresis; D015151:Immunoblotting; D008297:Male; D008757:Methylglucosides / Q000378:metabolism; D008833:Microcirculation; D051381:Rats; D011916:Rats, Inbred F344
D001786:Blood Glucose; D008757:Methylglucosides; D019325:3-O-Methylglucose; D003571:Cytochalasin B