Oxidative stress induces axonal beading in cultured human brain tissue.
Oxidative stress has been implicated in the pathogenesis of a number of human neurodegenerative disorders of the central nervous system (CNS), including Alzheimer's disease (AD). To better understand the pathological effects of oxidative stress on CNS neurons we used a primary human brain cell culture model of hydrogen peroxide-induced oxidative stress. Neuronal and astrocytic morphology was visualised by immunofluorescence with antibodies to the neuron-specific microtubule component beta-tubulin III and against glial fibrillary acidic protein (GFAP), respectively. After exposure to 40 mM H(2)O(2) for 60-90 min, axonal swelling was observed, which developed into axonal beading after 48 h. No beading was observed in GFAP-positive astrocytes. Despite the concentration of H(2)O(2) used, neurons remained attached to the substratum and showed no signs of apoptosis. This was attributed to the neuroprotective effect of the B-27 medium supplement, which contained antioxidants. The axonal swelling and beading was consistent with a disruption of microtubules by oxidative stress and subsequent hold-up of axonal transport.
Roediger
Ben
B
Neuroscience Unit, School of Biological Sciences A08, University of Sydney, 2006, Sydney, NSW, Australia.
Armati
Patricia J
PJ
D000975:Antioxidants / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology; D001369:Axons / Q000187:drug effects* / Q000473:pathology*; D002478:Cells, Cultured; D003470:Culture Media; D005333:Fetus; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D016877:Oxidants / Q000494:pharmacology*; D018384:Oxidative Stress; D016548:Prosencephalon / Q000187:drug effects / Q000473:pathology; D014404:Tubulin / Q000378:metabolism
D000975:Antioxidants; D003470:Culture Media; D005904:Glial Fibrillary Acidic Protein; D016877:Oxidants; D014404:Tubulin; D006861:Hydrogen Peroxide