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.
Brewer
G J
GJ
Southern Illinois University School of Medicine, Springfield 62794-9626, USA. gbrewer@siumed.edu
D000140:Acidosis, Lactic; D000367:Age Factors; D000375:Aging / Q000502:physiology; D016229:Amyloid beta-Peptides / Q000009:adverse effects*; D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants; D002470:Cell Survival; D002478:Cells, Cultured; D016222:Fibroblast Growth Factor 2; D018698:Glutamic Acid / Q000009:adverse effects*; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects / Q000196:embryology; D007150:Immunohistochemistry; D019344:Lactic Acid / Q000009:adverse effects*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D016875:tau Proteins / Q000378:metabolism
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D008869:Microtubule-Associated Proteins; D016875:tau Proteins; D016222:Fibroblast Growth Factor 2; D019344:Lactic Acid; D018698:Glutamic Acid