Oxidative stress has been implicated in the pathogenesis of several neurodegenerative disorders including Alzheimer's disease (AD). Increased lipid peroxidation, decreased levels of polyunsaturated fatty acids, and increased levels of 4-hydroxynonenal (HNE), F2-isoprostanes, and F4-neuroprostanes are present in the brain in patients with AD. Acrolein, an α,β-unsaturated aldehydic product of lipid peroxidation has been demonstrated to be approximately 100 times more reactive than HNE and is present in neurofibrillary tangles in the brain in AD. We recently demonstrated statistically significant elevated concentrations of extractable acrolein in the hippocampus/parahippocampal gyrus and amygdala in AD compared with age-matched control subjects. Concentrations of acrolein were two to five times those of HNE in the same samples. Treatment of hippocampal cultures with acrolein led to a time- and concentration-dependent decrease in cell survival as well as a concentration-dependent increase in intracellular calcium. In cortical neuron cultures, we now report that acrolein causes a concentration-dependent impairment of glutamate uptake and glucose transport in cortical neuron cultures. Treatment of cortical astrocyte cultures with acrolein led to the same pattern of impairment of glutamate uptake as observed in cortical neuron cultures. Collectively, these data demonstrate neurotoxicity mechanisms of arolein that might be important in the pathogenesis of neuron degeneration in AD. Copyright (C) 2000 Elsevier Science Inc.
|Number of pages||7|
|Journal||Free Radical Biology and Medicine|
|State||Published - Oct 15 2000|
Bibliographical noteFunding Information:
Funding for this work was provided by NIH grants 5-P01-AG05119 and 5-P50-AG05144 and by a grant from the Abercrombie Foundation. The authors thank Paula Thomason for editorial and Jane Meara for technical assistance in manuscript preparation.
- Alzheimer's disease
- Free radicals
- Lipid peroxidation
- Neuronal cultures
ASJC Scopus subject areas
- Physiology (medical)