Age-related changes in glutamate concentration and synaptosomal glutamate uptake in adult rat striatum

It has been suggested that Glutamate (Glu), which has neurotoxic properties and is thought to be the excitatory neurotransmitter release at corticostriatal synapses, might play a role in neurological disorders involving the striatum. To establish normative data which may serve as baseline for evaluating experimental evidence relevant to this proposal, we have studied Glu concentrations and synaptosomal Glu high affinity uptake kinetics in the striatum of male and female rats at various ages from 3 to 19 months. Here we report that all parameters studied (Glu levels, Vmax and Km of uptake) undergo significant changes with advancing age. Striatal Glu concentrations are consistently in the range of 12 mmol/kg wet weight in early adult life (3–6 months) but drop to 10 mmol/kg by 10 months and 9.6 mmol/kg by 19 months (an overall 20% decrease). Concomitantly, significant reductions in Vmax and km of the Glu high affinity transport system occur, suggesting an age-related loss in the number of high affinity Glu transport sites and a compensatory increase in affinity of remaining sites for Glu. Tentatively we propose that degenerative changes in the putatively glutamergic corticostriatal tract, as a normal aspect of aging, is the simplest and most likely explanation for the observed changes. If such changes with normal aging also occur in humans, this must be taken into consideration in the interpretation of studies pertaining to the possible role of Glu in neurological disorders.