SELECTIVE LOSS OF PHORBOL-12,13-DIBUTYRATE-FACILITATED L-GLUTAMATE TRANSPORT IN FOREBRAIN NEURONS OF AGED RATS

Phorbol-12,13-dibutyrate (PDBu), an activator of protein kinase C, was used to evaluate potential age-related changes in phosphorylation-dep endent facilitation of high-affinity L-glutamate uptake in the rat cen tral nervous system (CNS). Forebrain homogenates from male Fischer-344 /brown Norway Fl hybrid rats were separated into glio-enriched (glial plasmalemmal vesicles) and neuron-enriched fractions (synaptosomes) an d assayed for sodium-dependent transport of L-[H-3]glutamate. Glial fr actions from rats aged 5, 25, 31, and 37 months exhibited similar rate s of basal L-[H-3]glutamate transport and demonstrated no significant age-related differences with respect to the maximal facilitatory effec t of PDBu (1-100 mu M). In contrast, neuronal fractions exhibited an a ge-related decline ill both indices, with basal L-[H-3]glutamate trans port decreasing from 710 +/- 31 to 560 +/- 40 pmoL/mg protein/90 s for the 5- and 37-month groups, respectively (p < .03) and PDBu having a significantly attenuated effect in aged animals. Together, these resul ts provide support for the hypothesis that aging is associated with a decrease in the number of neuronal L-glutamate transporters as well as a diminished capacity to up-regulate these transporters through a pro tein kinase C-dependent pathway.