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.