کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6021374 1580632 2016 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Altered cholesterol biosynthesis causes precocious neurogenesis in the developing mouse forebrain
ترجمه فارسی عنوان
تغذیه بیوسیتیزه کلسترول سبب ایجاد نوروژنز پیش از قاعدگی در پیشانی مغز می شود
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی عصب شناسی
چکیده انگلیسی


- A recessive mutation in Hsd17b7rud causes precocious neural progenitor differentiation.
- Proliferation, polarity, and IKNM are disrupted in the Hsd17b7rud mutant forebrain.
- Hsd17b7rud mutant phenotypes are primarily due to altered cholesterol biosynthesis.
- In utero administration of statins and dietary cholesterol results in partial rescue.

We previously reported a mutation in the cholesterol biosynthesis gene, hydroxysteroid (17-beta) dehydrogenase 7 (Hsd17b7rudolph), that results in striking embryonic forebrain dysgenesis. Here we describe abnormal patterns of neuroprogenitor proliferation in the mutant forebrain, namely, a decrease in mitotic cells within the ventricular zone (VZ) and an increase through the remainder of the cortex by E11.5. Further evidence suggests mutant cells undergo abnormal interkinetic nuclear migration (IKNM). Furthermore, intermediate progenitors are increased at the expense of apical progenitors by E12.5, and post-mitotic neurons are expanded by E14.5. In vitro primary neuron culture further supports our model of accelerated cortical differentiation in the mutant. Combined administration of a statin and dietary cholesterol in utero achieved partial reversal of multiple developmental abnormalities in the Hsd17b7rudolph embryo, including the forebrain. These results suggest that abnormally increased levels of specific cholesterol precursors in the Hsd17b7rudolph embryo cause cortical dysgenesis by altering patterns of neurogenesis.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Disease - Volume 91, July 2016, Pages 69-82
نویسندگان
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