کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4177459 1276423 2015 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Neonatal Maternal Separation Alters the Capacity of Adult Neural Precursor Cells to Differentiate into Neurons Via Methylation of Retinoic Acid Receptor Gene Promoter
ترجمه فارسی عنوان
جدایی مادران نوزاد از ظرفیت سلول های پیشگیر عصبی بزرگسالان به منظور تشخیص به عصب ها از طریق متال سازی پروتئین گیرنده ی گیرنده اسید رتینوئیک
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی روانپزشکی بیولوژیکی
چکیده انگلیسی

BackgroundEarly life stress is thought to contribute to psychiatric disorders, but the precise mechanisms underlying this link are poorly understood. As neonatal stress decreases adult hippocampal neurogenesis, which, in turn, functionally contributes to many behavioral phenotypes relevant to psychiatric disorders, we examined how in vivo neonatal maternal separation (NMS) impacts the capacity of adult hippocampal neural precursor cells via epigenetic alterations in vitro.MethodsRat pups were separated from their dams for 3 hours daily from postnatal day (PND) 2 to PND 14 or were never separated from the dam (as control animals). We isolated adult neural precursor cells from the hippocampal dentate gyrus at PND 56 and assessed rates of proliferation, apoptosis, and differentiation in cell culture. We also evaluated the effect of DNA methylation at the retinoic acid receptor (RAR) promoter stemming from NMS on adult neural precursor cells.ResultsNMS attenuated neural differentiation of adult neural precursor cells but had no detectible effect on proliferation, apoptosis, or astroglial differentiation. The DNA methyltransferase (DNMT) inhibitor, 5-aza-dC, reversed a reduction by NMS of neural differentiation of adult neural precursor cells. NMS increased DNMT1 expression and decreased expression of RARα. An RARα agonist increased neural differentiation and an antagonist reduced retinoic acid-induced neural differentiation. NMS increased the methylated portion of RARα promoter, and the DNMT inhibitor reversed a reduction by NMS of RARα messenger RNA expression.ConclusionsNMS attenuates the capacity of adult hippocampal neural precursor cells to differentiate into neurons by decreasing expression of RARα through DNMT1-mediated methylation of its promoter.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biological Psychiatry - Volume 77, Issue 4, 15 February 2015, Pages 335–344
نویسندگان
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