کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6285725 | 1615177 | 2008 | 5 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Reduced brain volumes in mice expressing APP-Austrian mutation but not in mice expressing APP-Swedish-Austrian mutations
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
We previously described two transgenic mouse lines expressing sub-endogenous levels of the 'Austrian' APP-T714I mutation (driven by the prenatally active PDGF-β promoter; APP-Au mice) and showing intraneuronal Aβ pathology and reduced brain volumes on MRI at 12 and 20 months of age. To further investigate whether reduced brain sizes were caused by neurodegeneration or a neurodevelopmental defect, we now measured brain volumes as early as postnatal day 10. At this age, a distinguishable reduction in brain volumes was absent, indicating that brain volume deficits in APP-Au mice are not caused by a neurodevelopmental defect. To further study the association between intraneuronal Aβ and reduced brain volumes, we further generated and analyzed an APP transgenic mouse model expressing both Austrian and Swedish (K670N/M671L) mutations (APP-SwAu mice). APP-Swedish mutation is known to lead to altered APP processing in the secretory pathway, precluding its later processing in endosomal-lysosomal compartments, the site of intraneuronal Aβ accumulation. Also, to have higher levels of transgene expression only after birth, a murine Thy-1 promoter was utilized for APP-SwAu mouse lines. Despite having five times higher transgene APP levels compared to APP-Au mice, APP-SwAu mice showed significantly lower intraneuronal Aβ levels in the absence of reduced brain volumes, suggesting that intraneuronal Aβ accumulation is related to reduced brain volumes in APP-Au mice. These data also provide a first in vivo indication of altered processing of APP-Swedish at sub-endogenous levels, an effect not observed in mouse models expressing the APP-Swedish mutation in high amounts.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience Letters - Volume 447, Issues 2â3, 12 December 2008, Pages 143-147
Journal: Neuroscience Letters - Volume 447, Issues 2â3, 12 December 2008, Pages 143-147
نویسندگان
Bianca Van Broeck, Greet Vanhoutte, Ivy Cuijt, Sandra Pereson, Geert Joris, Jean-Pierre Timmermans, Annemie Van der Linden, Christine Van Broeckhoven, Samir Kumar-Singh,