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-dependent facilitation of high-affinity L-glutamate uptake in the rat central nervous system (CNS). Forebrain homogenates from male Fischer-344/brown Norway F1 hybrid rats were separated into glia-enriched (glial plasmalemmal vesicles) and neuron-enriched fractions (synaptosomes) and assayed for sodium-dependent transport of L-[3H]glutamate. Glial fractions from rats aged 5, 25, 31, and 37 months exhibited similar rates of basal L-[3H]glutamate transport and demonstrated no significant age-related differences with respect to the maximal facilitatory effect of PDBu (1-100 microM). In contrast, neuronal fractions exhibited an age-related decline in both indices, with basal L-[3H]glutamate transport 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 results 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 protein kinase C-dependent pathway.
Daniels
K K
KK
Department of Neuroscience, University of Florida, Gainesville 32610-0144, USA.
Vickroy
T W
TW
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism*; D006824:Hybridization, Genetic; D008297:Male; D009474:Neurons / Q000378:metabolism*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology*; D016548:Prosencephalon / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344
D015240:Phorbol 12,13-Dibutyrate; D018698:Glutamic Acid