قرار گرفتن در معرض اسید والپروئیک در دوران بارداری، باعث افزایش تحریک پذیری در هیپوکامپ موش های پس از تولد می شود
|کد مقاله||سال انتشار||تعداد صفحات مقاله انگلیسی||ترجمه فارسی|
|160574||2018||33 صفحه PDF||سفارش دهید|
Publisher : Elsevier - Science Direct (الزویر - ساینس دایرکت)
Journal : NeuroToxicology, Volume 65, March 2018, Pages 1-8
Prenatal valproic acid (VPA) exposure is a well-known animal model of autism spectrum disorder (ASD) that produces alterations in embryonic and adult neurogenesis as well as adolescent/adulthood neurobehavioral phenotypes. However, the effects of prenatal VPA exposure on neural network excitability, especially during the synaptogenic period around eye opening, are not fully understood. In this study, we orally administered VPA (300â¯mg/kg) to pregnant Wistar rats on gestation day 15 and subsequently performed field potential recording in the CA1 area of hippocampal slices obtained from control (saline-exposed) and VPA-exposed rat pups between postnatal day (PND) 13 and PND18. In control slices, we observed an abrupt enhancement of stimulation-dependent responses including population spike (PS) amplitudes and field excitatory postsynaptic potential (fEPSP) slopes at PND16, which coincided with the average day of eye opening. In contrast, VPA-exposed pups exhibited delayed eye opening (PND17) and gradual rather than abrupt increases in PS amplitudes and fEPSP slopes over the duration of the synaptogenic period. We next investigated the involvement of ambient GABA (Î³-aminobutyric acid) in PS generation using bicuculline methiodide (BMI), a GABA type A (GABAA) receptor antagonist. In control slices, BMI enhanced PS amplitudes during PND14â15 (before eye opening) and had little effect thereafter during PND16â17; a subsequent regression model analysis of BMI ratios (the ratio of PS amplitudes in the presence and absence of BMI) indicated a possible developmental change between these periods. In contrast, almost identical regression models were obtained for BMI ratios during PND14â15 and PND16â17 in the VPA-exposed group, indicating the absence of a developmental change. Our results suggest that prenatal VPA exposure accelerates the development of hippocampal excitability before eye opening. Moreover, our experimental model can be used as a novel approach for the evaluation of developmental neurotoxicity.