کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4328648 1614184 2009 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Characterization of mutant mice that express polyglutamine in cerebellar Purkinje cells
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
Characterization of mutant mice that express polyglutamine in cerebellar Purkinje cells
چکیده انگلیسی

We recently produced transgenic mice that expressed an abnormally expanded polyglutamine (polyQ) specifically in cerebellar Purkinje cells (polyQ mice). The polyQ mice showed inclusion body formation, cerebellar atrophy and severe ataxia. Here we analyzed polyQ mice using immunohistochemistry, immunoelectronmicroscopy and electrophysiology. A diffuse form of polyQ was detected in the nucleus. Interestingly, ubiquitinated large inclusions were located close to, but apparently outside of the soma of Purkinje cells. Infusion of lucifer yellow into Purkinje cells clearly indicated the traffic between the periplasmic inclusions and soma of Purkinje cells. To examine whether the formation of periplasmic inclusions was an active process or a result of cell death, the polyQ mouse cerebellum was immunolabeled for cleaved caspase-3, a marker of apoptosis. Interestingly, no Purkinje cells in P80 polyQ mice immunoreacted with the antibody. The results were substantiated by electrophysiological assay, which showed that P80 Purkinje cells with large periplasmic inclusions were functionally active: excitatory postsynaptic currents (EPSCs) were reliably evoked upon electrical stimulation of parallel fibers (PFs) or climbing fibers (CFs), and current injection into Purkinje cells generated action potentials; however, the frequency of action potentials in response to various volumes of current injection was consistently lower in polyQ mice than in wild-type animals, and aberrant innervation by multiple CFs was detected in polyQ mouse Purkinje cells. These results suggest that Purkinje cells with periplasmic inclusions were not apoptotic, but their functions were substantially impaired, which could contribute to the severe ataxic phenotype.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Brain Research - Volume 1255, 19 February 2009, Pages 9–17
نویسندگان
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