Growth Factors Prevent Mitochondrial Dysfunction, Loss of Calcium Homeostasis, and Cell Injury, but Not ATP Depletion in Hippocampal Neurons Deprived of Glucose

摘要: The mechanism of growth factor protection against metabolic/excitotoxic insults was examined. time course changes in ATP levels, mitochondrial transmembrane potential, intracellular free calcium levels ([Ca2+]i), and cell survival resulting from glucose deprivation were assessed cultured hippocampal neurons. significantly reduced within 1 h the onset reached less than 20% control by 12 h. Mitochondrial potential (assessed rhodamine 123 accumulation mitochondria) declined progressively between 4 20 following deprivation. [Ca2+]i during first deprivation, gradually rose through h, then rapidly elevated five- to sevenfold after 16 did not increase, dysfunction damage prevented, hypoglycemic neurons incubated Ca(2+)-deficient medium. Elevation exposure glutamate caused loss fluorescence structural mitochondria. function could be restored maintained addition prior late elevation [Ca2+]i. Nerve (NGF), basic fibroblast (bFGF), insulin-like II (IGF-II) prevented both homeostasis protected injury, but prevent hypoglycemia-induced reduction levels. NaCN 2,4-dinitrophenol (DNP) a large [Ca2+]i, dysfunction, death. NGF, bFGF, IGF-II each adverse effects DNP on function, survival. Loss may critical event leading death energy failure. Preventing general for neuroprotective action factors.