کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4331489 1614300 2007 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Normal electrical properties of hippocampal neurons modelling early Huntington disease pathogenesis
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
Normal electrical properties of hippocampal neurons modelling early Huntington disease pathogenesis
چکیده انگلیسی

Huntington disease (HD) is a neurodegenerative disorder caused by an unstable and progressive expansion of a CAG trinucleotide repeat tract in the HD gene. Previous studies using truncated forms of the HD gene have shown pronounced deficits in synaptic transmission and plasticity but rather modest changes in intrinsic cellular properties, despite overt pathology. The knock-in mice carrying a 72–80 CAG repeat mutation is an accurate genetic model of early stage HD, displaying a more subtle disease phenotype. To relate full-length HD gene expression and differential polyglutamine expansion with possible pathophysiological changes in salient electrophysiological properties of neurons that may underlie early symptoms of HD, including mood and cognitive impairments, we have conducted whole-cell recordings from hippocampal area CA1 pyramidal cells in Hdh6/Q72 and Hdh4/Q80 knock-in mice. Electrophysiological characterisation of cells obtained from young adult (< 4 months) HD mice harbouring an expanded CAG repeat stretch and age-matched wild type (WT) mice revealed no significant differences in any of the active or passive membrane properties investigated. Similar findings, showing a lack of significant differences in cellular electrical properties, were obtained from cells of aged (> 18 months) HD mice and WT controls, despite modest levels of repeat length variability demonstrated by single cell PCR. Thus, the current study indicates a lack of overt changes in the electrical membrane properties of pyramidal cells in HD mice accurately modelling early stage HD pathology. Furthermore, together with our previous work, these findings point to a synaptic rather than cellular locus of HD-related pathology.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Brain Research - Volume 1139, 30 March 2007, Pages 226–234
نویسندگان
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