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Severe motor neuron degeneration in the spinal cord of the Tg2576 mouse model of Alzheimer disease

Title
Severe motor neuron degeneration in the spinal cord of the Tg2576 mouse model of Alzheimer disease
Authors
Seo J.-S.Leem Y.-H.Lee K.-W.Kim S.-W.Lee J.-K.Han P.-L.
Ewha Authors
한평림이강우
SCOPUS Author ID
한평림scopus
Issue Date
2010
Journal Title
Journal of Alzheimer's Disease
ISSN
1387-2877JCR Link
Citation
vol. 21, no. 1, pp. 263 - 276
Indexed
SCIE; SCOPUS WOS scopus
Abstract
The transgenic mouse Tg2576 is widely used as a murine model of Alzheimer's disease (AD) and exhibits plaque pathogenesis in the brain and progressive memory impairments. Here we report that Tg2576 mice also have severe spinal cord deficits. At 10 months of age, Tg2576 mice showed a severe defect in the hindlimb extension reflex test and abnormal body trembling and hindlimb tremors when suspended by the tail. The frequency and severity of these abnormalities were overt at 10 months of age and became gradually worsened. On the foot-printing analysis, Tg2576 mice had shorter and narrower strides than the non-transgenic control. Histological analyses showed that neuronal cells including cholinergic neurons in the lumbar cord of Tg2576 mice were severely reduced in number. At 16 months of age, Tg2576 mice showed high levels of amyloid-β accumulation in the spinal cord. Consistent with this, Tg2576 mice showed that lipid peroxidation levels were increased and mitochondrial metabolic activity were significantly reduced in the spinal cord. Administration of curcumin, a natural compound that has antioxidant properties, notably reversed motor function deficits of Tg2576 mice. The enhanced lipid peroxidation and neuronal loss in the lumbar cord was also partially suppressed by curcumin. Electron microscopic analysis revealed that the sciatic nerve fibers were severely reduced in number and were demyelinated in Tg2576 mice, which were partially rescued by curcumin. These results showed that Tg2576 mice display severe degeneration of motor neurons in the spinal cord and associated motor function deficits. © 2010 IOS Press.
DOI
10.3233/JAD-2010-091528
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일반대학원 > 뇌·인지과학과 > Journal papers
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