Early degenerative changes in transgenic mice expressing mutant huntingtin involve dendritic abnormalities but no impairment of mitochondrial energy production

Paolo Guidetti, Vinod Charles, Er Yun Chen, P. Hemachandra Reddy, Jeffrey H. Kordower, William O. Whetsell, Robert Schwarcz, Danilo A. Tagle

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    Abstract

    Mitochondrial defects, which occur in the brain of late-stage Huntington's disease (HD) patients, have been proposed to underlie the selective neuronal loss in the disease. To shed light on the possible role of mitochondrial energy impairment in the early phases of HD pathophysiology, we carried out Golgi impregnation and quantitative histochemical/biochemical studies in HD full-length cDNA transgenic mice that were symptomatic but had not developed to a stage in which neuronal loss could be documented. Golgi staining showed morphologic abnormalities that included a significant decrease in the number of dendritic spines and a thickening of proximal dendrites in striatal and cortical neurons. In contrast, measurements of mitochondrial electron transport Complexes I-IV did not reveal changes in the striatum and cerebral cortex in these mice. Examination of the neostriatum and cerebral cortex in human presymptomatic and pathological Grade 1 HD cases also showed no change in the activity of mitochondrial Complexes I-IV. These data suggest that dendritic alterations precede irreversible cell loss in HD, and that mitochondrial energy impairment is a consequence, rather than a cause, of early neuropathological changes.

    Original languageEnglish (US)
    Pages (from-to)340-350
    Number of pages11
    JournalExperimental Neurology
    Volume169
    Issue number2
    DOIs
    StatePublished - Jan 1 2001

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    Keywords

    • Dendrites
    • Golgi
    • Huntington's
    • Mitochondrial
    • Mouse
    • Neurodegeneration
    • Striatum
    • Transgenic

    ASJC Scopus subject areas

    • Neurology
    • Developmental Neuroscience

    Cite this

    Guidetti, P., Charles, V., Chen, E. Y., Reddy, P. H., Kordower, J. H., Whetsell, W. O., Schwarcz, R., & Tagle, D. A. (2001). Early degenerative changes in transgenic mice expressing mutant huntingtin involve dendritic abnormalities but no impairment of mitochondrial energy production. Experimental Neurology, 169(2), 340-350. https://doi.org/10.1006/exnr.2000.7626