Journals of Gerontology Series A: Biological Sciences and Medical Sciences, Vol 53, Issue 6 B449-B451, Copyright © 1998 by The Gerontological Society of America
Selective loss of phorbol-12,13-dibutyrate-facilitated L-glutamate transport in forebrain neurons of aged rats
KK Daniels and TW Vickroy
Department of Neuroscience, University of Florida, Gainesville 32610- 0144, USA.
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.
