کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6282031 1615130 2014 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Valproic acid selectively suppresses the formation of inhibitory synapses in cultured cortical neurons
ترجمه فارسی عنوان
اسید و والپروئیک به طور انتخابی باعث تشکیل سیناپس مهارکننده در نورونهای کورتنی می شود
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
چکیده انگلیسی
Valproic acid (VPA) has been used to treat epileptic patients because of its ability to potentiate GABA signaling in the brain. Despite its clinical significance, VPA administration during pregnancy increases the risk of congenital abnormalities, such as neural tube defects and neurodevelopmental disorders including autism. Furthermore, recent studies revealed that early postnatal administration of VPA also leads to neurodevelopmental deficits in rodents. Here, using cultured cortical neurons derived from postnatal day 1 rats, we examined whether exposure to VPA would affect synapse formation. When neurons were exposed to 1 mM VPA during early development, expression of the vesicular GABA transporter (VGAT) was selectively reduced, whereas other synaptic markers, including the vesicular glutamate transporters 1 and 2 (VGLUT1 and 2), were not affected. This VPA effect was mediated through inhibition of histone deacetylases (HDACs), since the effects were mostly recapitulated by an HDAC inhibitor, trichostatin A, but not by a VPA derivative, valpromide, which lacks HDAC inhibitor activity. Immunocytochemical analysis demonstrated that VPA exposure resulted in a retardation of axonal growth specific to GABAergic neurons and a decrease in VGAT-positive synapses. Since disturbance of the excitatory and inhibitory (E-I) balance has been implicated as a potential cause of multiple psychiatric disorders, our results may account for one of the cellular mechanisms underlying the pathogenesis of VPA-induced neurodevelopmental impairments.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience Letters - Volume 569, 21 May 2014, Pages 142-147
نویسندگان
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