Endogenous glutamate release from frontal cortex of adult and aged rats

Glutamate (GLU) is a major excitatory neurotransmitter in the frontal cortex. Alterations in GLU neurotransmission are present in a number of neurodegenerative diseases, however, little is known about the normal aging process of GLU utilizing neurons. GLU release, uptake and content were examined in the frontal cortex of adult (6 months old) and aged (24 months old) male, Fisher 344 rats. These markers were used to assess the functional integrity of intrinsic and extrinsic GLU utilizing pathways innervating the frontal cortex. Basal- and potassium- (56 mM) evoked GLU release from brain slices of aged rats were not significantly different from that of adults. Kainic acid (1.0 mM) failed to significantly augment basal or potassium-stimulated GLU release in the frontal cortex of either aged or adult rats. Uptake of [3H] GLU into brain slices was also unaltered as a function of age. In contrast, GLU content was decreased 17% in the frontal cortex of aged rats when compared to the adults. These results suggest that the functional integrity of GLU utilizing nerve terminals in the frontal cortex is maintained in 24-month-old Fisher 344 rats. The decrease in GLU content may reflect a generalized neuronal loss or a defect in neuronal and/or glial GLU metabolism in the metabolic compartment.