EFFECT OF AGING ON THE KINETICS OF BLOOD-BRAIN-BARRIER UPTAKE OF TRYPTOPHAN IN RATS

Purpose. The purpose of this investigation was to examine the effect o f aging on the blood-brain barrier (BBB) transport of tryptophan. Meth ods. A well established in-situ brain perfusion technique was used to examine brain uptake of C-14-tryptophan in 2-, 12- and 24-month old Sp rague-Dawley rats; perfusate tryptophan concentrations ranged from 0.0 0175 to 2 mM. Uptake data were modeled using non-linear regression ana lysis. Results. Permeability-surface area product (PA) for tryptophan was significantly lower in 12- and 24-month old rats, as compared to t he 2-month old animals. A transport model consisting of both saturable (Michaelis-Menten type) and non-saturable components best described b rain uptake of tryptophan in all 3 age groups. However, age-dependent differences in BBB transport parameters of tryptophan were observed. F or the saturable component, both Vmax and Km were significantly lower in the 12- and 24-month old rats, as compared to the youngest group of rats. These results suggest that transporter mobility, number and aff inity for tryptophan are altered in older rats. Values for K-d, the ra te constant for nan-saturable brain tryptophan transport, were also si gnificantly lower in animals of the two older age groups. Interestingl y, PA values for thiourea, a compound believed to be transported acros s BBB by diffusion, were also lower in these two age groups. Conclusio ns. Aging decreases the ability of the BBB to transport the neutral am ino acid tryptophan.