AGE-RELATED-CHANGES IN GLUTAMATE CONCENTRATION AND SYNAPTOSOMAL GLUTAMATE UPTAKE IN ADULT-RAT STRIATUM

Glutamate (Glu), which has neurotoxic properties and is presumably the excitatory neurotransmitter released at corticostriatal synapses, may play a role in neurological disorders involving the striatum. Glu concentrations and synaptosomal Glu high-affinity uptake kinetics were studied to establish normative values in the striatum of male and female rats, at various ages from 3-19 mo. The parameters (Glu levels, Vmax and Km of uptake) underwent significant changes with age. Striatal Glu concentrations were consistently in the range of 12 mmol/kg wet wt in early adult life (3-6 mo.), but dropped to 10 mmol/kg by 10 mo. and 9.6 mmol/kg by 10 mo. (an overall 20% decrease). Concomitantly, significant reductions in Vmax and Km of the Glu high-affinity transport system occurred, 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. Degenerative changes in the putatively glutamergic corticostriatal tract, as a normal aspect of aging, probably occur. If these changes with normal aging occur in humans, they require consideration for interpretation of the possible role of Glu in neurological disorders.