Age-related changes in the uptake and release of glutamate and aspartate in the mouse brain.

The studies were carried out on 3- and 7-day, 3-, 6-, 12-, 18- and 24-month-old mice. The levels of glutamate and aspartate increased in most brain areas in developing mice and then decreased gradually during ageing, the changes depending, however, on the brain region. The maximal velocity (V) of high-affinity uptake of [3H]glutamate was markedly reduced in cerebral cortical synaptosomes at the age of 24 months, indicating an age-related loss in the number of transport sites. The transport constant (Km) was also diminished in aged mice, indicating a compensatory increase in the affinity of the remaining transport sites. The basal and K(+)-stimulated (50 mM) release of endogenous glutamate and aspartate varied depending on the brain region. The responses to K+ stimulation generally increased during maturation, whereas the other age-related changes were more variable. The basal unstimulated release of glutamate remained fairly constant in the cerebral cortex during ageing, but K+ depolarization liberated more glutamate in 24-month-olds than in 3-month-olds. The decreased uptake capacity together with an increased release of glutamate may contribute to the degenerative changes associated with normal brain ageing and also to the pathogenesis of age-related neurodegenerative disorders.