| Early vacuolization and mitochondrial damage in motor neurons of FALS mice are not associated with apoptosis or with changes in cytochrome oxidase histochemical reactivity. | |
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MedLine Citation:
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PMID: 11676989 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Overexpression of mutated superoxide dismutase (SOD1) in transgenic mice causes a progressive motor neuron degeneration in the spinal cord similar to that in human amyotrophic lateral sclerosis (ALS). Ultrastructural analysis of motor neurons at different stages of the disease in transgenic C57BL/6 mice carrying the G93A mutation of SOD1 showed, at about 2 weeks of age, much earlier than the initial symptoms of the disease, microvacuoles in the cytoplasm, with marked swelling of the mitochondria. Nuclei with an apoptotic morphology were never observed in these motor neurons. Swollen mitochondria were also seen in the distal part of motor axons of phrenic nerves and in the large axons of sciatic nerves before the onset of the disease, but no mitochondrial alterations were seen in skeletal muscles or in the small sciatic nerve axons. Moreover, we found no apparent changes in the histochemical reactivity of cytochrome oxidase in motor neurons of transgenic mice even at the advanced stage of the disease, suggesting that partial neuronal activity in these cells may be maintained despite the altered mitochondria. Immunoreactivity for human SOD1 was high around vacuoles in the motor neurons of transgenic mice but no cytoplasmic intracellular SOD1 aggregates were observed. Our data indicate that mitochondrial swelling may be an important factor triggering the cascade leading to progressive motor neuron death. Activation of the mitochondrial permeability transition pore may be involved in this process, through excitotoxicity or other neurotoxic stimuli. |
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Authors:
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C Bendotti; N Calvaresi; L Chiveri; A Prelle; M Moggio; M Braga; V Silani; S De Biasi |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of the neurological sciences Volume: 191 ISSN: 0022-510X ISO Abbreviation: J. Neurol. Sci. Publication Date: 2001 Oct |
Date Detail:
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Created Date: 2001-10-25 Completed Date: 2002-01-30 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0375403 Medline TA: J Neurol Sci Country: Netherlands |
Other Details:
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Languages: eng Pagination: 25-33 Citation Subset: IM |
Affiliation:
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Laboratory of Molecular Neurobiology, Department of Neuroscience, Istituto di Ricerche Farmacologiche "Mario Negri," Via Eritrea 62, 20157, Milan, Italy. Bendotti@marionegri.it |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amyotrophic Lateral Sclerosis
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enzymology*,
genetics,
pathology Animals Apoptosis* Disease Models, Animal Disease Progression Electron Transport Complex IV / metabolism* Humans Immunohistochemistry Lumbosacral Region Mice Mice, Inbred C57BL Mice, Transgenic Mitochondria / enzymology, pathology* Motor Neurons / enzymology*, pathology Muscle, Skeletal / ultrastructure Phrenic Nerve / pathology, ultrastructure Spinal Cord / pathology, ultrastructure Succinate Dehydrogenase / metabolism Superoxide Dismutase / genetics, metabolism Vacuoles / pathology*, ultrastructure |
| Chemical | |
Reg. No./Substance:
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EC 1.15.1.-/superoxide dismutase 1; EC 1.15.1.1/Superoxide Dismutase; EC 1.3.99.1/Succinate Dehydrogenase; EC 1.9.3.1/Electron Transport Complex IV |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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