Abstract
BackgroundDuring 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.MethodsBlood 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.ResultsSVAT-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.ConclusionVariant 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.
Highlights
During intrauterine development, the formation and function of synaptic vesicles (SVs) are thought to be fundamental conditions essential for normal development of the brain
Expression of exosomal Synaptic vesicles (SVs)-associated transcripts (SVATs) in Autism spectrum disorder (ASD) Previously, we determined the differential expression of SVATs in peripheral blood lymphocytes of children with autism [16]
We have successfully replicated the differential expression of six SVAT pairs in peripheral lymphocytes and in circulating EXs isolated from peripheral plasma
Summary
The formation and function of synaptic vesicles (SVs) are thought to be fundamental conditions essential for normal development of the brain. Fang et al J Transl Med (2021) 19:154 serves as a helpful tool to probe into the mechanism underlying brain function; it is crucial to take into consideration the limitations of the concept when assessing the function of synapses in neurologic processing. Chemical transmission involves complex presynaptic molecular machinery that controls the release of neurotransmitters in an orderly manner when an action potential is fired at the synaptic terminal. SVs contain synaptic vesicle–associated transcripts (SVATs) and synaptic vesicle-associated proteins (SVAPs), which have a variety of functions, including the following functions: ion channels; scaffolding proteins; neurotransmitter receptors; and facilitating synaptic cell adhesion. Few studies have investigated the mechanisms that induce synaptic neurotransmission and the relationship with many neurologic diseases [6]
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