Autism-associated synaptic vesicle transcripts are differentially expressed in maternal plasma exosomes of physiopathologic pregnancies.

Autism-associated synaptic vesicle transcripts are differentially expressed in maternal plasma exosomes of physiopathologic pregnancies.
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自闭症相关突触囊泡转录物在生理性妊娠的母体血浆外泌体中有差异表达。

DOI:
10.1186/s12967-021-02821-6
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发表时间:
2021-04-15
影响因子:
7.4
通讯作者:
Zhong N
Zhong N
中科院分区:
医学2区
文献类型:
--
作者:
Fang Y;Wan C;Wen Y;Wu Z;Pan J;Zhong M;Zhong N

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在子宫内发育过程中,突触小泡(SV)的形成和功能被认为是大脑正常发育所必需的基本条件。宫内期间缺乏先进的技术,例如对 SV 相关转录本 (SVAT)(包括六对 lncRNA-mRNA)的纵向实时监测,限制了对 SVAT 动态基因表达谱 (GEP) 的获取。我们之前报道了自闭症儿童外周血中 SVAT 的差异表达。本研究旨在确定来自自闭症儿童和不同胎龄孕妇的循环外泌体(EX)中差异表达的 SVAT 的动态特征。从患有变异生理病理妊娠的自闭症儿童和妇女中采集血液样本。使用 ExoQuick 外泌体沉淀试剂盒分离 EX,并通过透射电子显微镜 (TEM)、纳米颗粒跟踪分析 (NTA) 和蛋白质印迹进行表征。使用实时 PCR 对 lncRNA 和 lncRNA 靶向 mRNA 的表达进行定量。在自闭症儿童中检测到了 SVAT 相关的 lncRNA-mRNA,并且从妊娠早期到分娩期间存在差异表达。将病理性妊娠,包括自发性早产 (sPTB)、先兆子痫 (PE) 和妊娠期糖尿病 (GDM) 与正常生理性妊娠进行比较,结果显示 STX8、SLC18A2 和 SYP 的 SVAT-lncRNA 和 SVAT-mRNA 与 sPTB 之间存在特定相关性;具有PE的STX8的SVAT-lncRNA和SVAT-mRNA; SV2C 的 SVAT-lncRNA 和 SVAT-mRNA 以及患有 GDM 的 SYP 的 SVAT-mRNA。病理妊娠的各种并发症可能会改变 SVAT 的 GEP,这可能会影响宫内神经回路的发育,从而影响胎儿的大脑发育。在线版本包含可在 10.1186/s12967-021-02821-6 获取的补充材料。
During intrauterine development, the formation and function of synaptic vesicles (SVs) are thought to be fundamental conditions essential for normal development of the brain. Lacking advanced technology during the intrauterine period, such as longitudinal real-time monitoring of the SV-associated transcripts (SVATs), which include six pairs of lncRNA-mRNA, has limited acquisition of the dynamic gene expression profile (GEP) of SVATs. We previously reported the differential expression of SVATs in the peripheral blood of autistic children. The current study was designed to determine the dynamic profiles of differentially-expressed SVATs in circulating exosomes (EXs) derived from autistic children and pregnant women at different gestational ages. Blood samples were collected from autistic children and women with variant physiopathologic pregnancies. EXs were isolated with an ExoQuick Exosome Precipitation Kit and characterized by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blotting. The expression of lncRNAs and lncRNA-targeted mRNAs were quantified using real-time PCR. SVAT-associated lncRNAs-mRNAs were detected in autistic children and differentially expressed from the first trimester of pregnancy to the term of delivery. Pathologic pregnancies, including spontaneous preterm birth (sPTB), preeclampsia (PE), and gestational diabetes mellitus (GDM), were compared to normal physiologic pregnancies, and shown to exhibit specific correlations between SVAT-lncRNA and SVAT-mRNA of STX8, SLC18A2, and SYP with sPTB; SVAT-lncRNA and SVAT-mRNA of STX8 with PE; and SVAT-lncRNA and SVAT-mRNA of SV2C as well as SVAT-mRNA of SYP with GDM. Variant complications in pathologic pregnancies may alter the GEP of SVATs, which is likely to affect the intrauterine development of neural circuits and consequently influence fetal brain development. The online version contains supplementary material available at 10.1186/s12967-021-02821-6.
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