Disruption of Purkinje cell function prior to huntingtin accumulation and cell loss in an animal model of Huntington disease.

Experimental Neurology
S E DoughertyR M Cowell

Abstract

Huntington Disease (HD) is a devastating neurological disorder characterized by progressive deterioration of psychiatric, motor, and cognitive function. Purkinje cells (PCs), the output neurons of the cerebellar cortex, have been found to be vulnerable in multiple CAG repeat disorders, but little is known about the involvement of PC dysfunction in HD. To investigate possible PC abnormalities, we performed quantitative real time PCR, Western blot analysis, and immunohistochemistry experiments to explore the changes in PC markers in the R6/2 mouse model of severe HD. There were reductions in the transcript and protein levels of the calcium-binding proteins parvalbumin and calbindin, as well as the enzyme glutamic acid decarboxylase 67. Immunohistochemistry supported these results, with the most substantial changes occurring in the PC layer. To determine whether the reductions in PC marker expression were due to cell loss, we performed stereology on both presymptomatic and end-stage R6/2 mice. Stereological counts indicated a significant reduction in PC number by end-stage but no change in presymptomatic animals (4 weeks of age). To assess cellular function prior to cell loss and symptom onset, we measured spontaneous firing in PC...Continue Reading

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Citations

Jul 6, 2014·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Ravi Chopra, Vikram G Shakkottai
Dec 1, 2012·Experimental Neurology·S E DoughertyR M Cowell
Sep 16, 2014·Future Neurology·Ravi Chopra, Vikram G Shakkottai
Jan 23, 2015·Frontiers in Cellular Neuroscience·Elizabeth K LucasRita M Cowell
Sep 5, 2018·Journal of the American Veterinary Medical Association·Lorenzo MariLuisa De Risio
Apr 23, 2020·Frontiers in Neuroscience·Polina A EgorovaIlya B Bezprozvanny
Aug 4, 2018·Proteomes·Marcia RoySeth G N Grant

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