Age-related toxicity to lactate, glutamate, and beta-amyloid in cultured adult neurons.

The age-related susceptibility of the brain to neurodegenerative disease may be inherent in the susceptibility of individual neurons to various stressors. Neurons were isolated from embryonic, young- and old-aged rat hippocampus, cultured in serum-free medium and exposed to lactic acid, glutamate or beta-amyloid. Yields of isolated adult cells were 1 million cells/hippocampus, 12,000 cells/mg tissue, independent of age. For lactic acidosis, there was a non-significant 10% increment in killing of neuron-like cells from old rats compared to young. For glutamate, there was a 5-10% increment in killing of neuron-like cells from old rats compared to young rats and embryonic neurons. For cells exposed to the toxic fragment of beta-amyloid, A beta (25-35), toxicity was age, dose and time-dependent. Maximum toxicity in cells treated for 1 day with 25 microM A beta (25-35) was 16%, 24%, and 33% for embryonic, young and old cells. Similar results were found for A beta (1-40) (LD50 = 2 microM). These results suggest that aging imparts to individual cells an increased susceptibility to toxic substances relevant to neurodegenerative diseases.