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Molecular Autism

, 8:33

First Online: 28 June 2017Received: 01 August 2016Accepted: 09 June 2017


BackgroundMicroRNAs, small non-coding RNAs, are highly expressed in the mammalian brain, and the dysregulation of microRNA levels may be involved in neurodevelopmental disorders such as autism spectrum disorder ASD. In the present study, we examined whether prenatal valproic acid VPA exposure affects levels of microRNAs, especially the brain specific and enriched microRNAs, in the mouse embryonic brain.

ResultsPrenatal exposure to VPA at E12.5 immediately increased miR-132 levels, but not miR-9 or miR-124 levels, in the male embryonic brain. Prenatal exposure to VPA at E12.5 also increased miR-132 levels in the female embryonic brain. We further found that the prenatal exposure to VPA at E12.5 increased mRNA levels of Arc, c-Fos and brain-derived neurotrophic factor in both male and female embryonic brains, prior to miR-132 expression. In contrast, prenatal exposure to VPA at E14.5 did not affect miR-132 levels in either male or female embryonic brain. The prenatal VPA exposure at E12.5 also decreased mRNA levels of methyl-CpG-binding protein 2 and Rho GTPase-activating protein p250GAP, both of which are molecular targets of miR-132. Furthermore, RNA sequence analysis revealed that prenatal VPA exposure caused changes in several microRNA levels other than miR-132 in the embryonic whole brain.

ConclusionsThese findings suggest that the alterations in neuronal activity-dependent microRNAs levels, including an increased level of miR-132, in the embryonic period, at least in part, underlie the ASD-like behaviors and cortical pathology produced by prenatal VPA exposure.

KeywordsAutism mouse model Valproic acid MicroRNA Embryonic brain AbbreviationsASDAutism spectrum disorder

BDNFBrain-derived neurotrophic factor

FDRFalse discovery rate

MeCP2Methyl-CpG-binding protein 2

VPAValproic acid

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Autor: Yuta Hara - Yukio Ago - Erika Takano - Shigeru Hasebe - Takanobu Nakazawa - Hitoshi Hashimoto - Toshio Matsuda - Kazuhiro 


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