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精氨酸加压素对自闭症模型大鼠前额叶皮质转录组的影响。

Effects of arginine vasopressin on the transcriptome of prefrontal cortex in autistic rat model.

机构信息

State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guizhou, China.

Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guizhou Medical University, Guizhou, China.

出版信息

J Cell Mol Med. 2022 Nov;26(21):5493-5505. doi: 10.1111/jcmm.17578. Epub 2022 Oct 14.

Abstract

Our previous studies have also demonstrated that AVP can significantly improve social interaction disorders and stereotypical behaviours in rats with VPA-induced autism model. To further explore the mechanisms of action of AVP, we compared the PFC transcriptome changes before and after AVP treatment in VPA-induced autism rat model. The autism model was induced by intraperitoneally injected with VPA at embryonic day 12.5 and randomly assigned to two groups: the VPA-induced autism model group and the AVP treatment group. The AVP treatment group were treated with intranasal AVP at postnatal day 21 and for 3 weeks. The gene expression levels and function changes on the prefrontal cortex were measured by RNA-seq and bioinformatics analysis at PND42 and the mRNA expression levels of synaptic and myelin development related genes were validated by qPCR. Our results confirmed that AVP could significantly improve synaptic and axon dysplasia and promote oligodendrocyte development in the prefrontal cortex in VPA-induced autism models by regulating multiple signalling pathways.

摘要

我们之前的研究还表明,AVP 可以显著改善 VPA 诱导的自闭症模型大鼠的社交互动障碍和刻板行为。为了进一步探索 AVP 的作用机制,我们比较了 AVPA 治疗前后 VPA 诱导的自闭症大鼠模型前额叶皮质转录组的变化。自闭症模型通过在胚胎第 12.5 天腹腔内注射 VPA 诱导,随机分为两组:VPA 诱导的自闭症模型组和 AVP 治疗组。AVP 治疗组在出生后第 21 天开始经鼻内给予 AVP,并持续 3 周。在 PND42 时通过 RNA-seq 和生物信息学分析测量前额叶皮质的基因表达水平和功能变化,并通过 qPCR 验证突触和髓鞘发育相关基因的 mRNA 表达水平。我们的结果证实,AVP 通过调节多种信号通路,可显著改善 VPA 诱导的自闭症模型前额叶皮质中的突触和轴突发育不良,并促进少突胶质细胞的发育。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d667/9639040/156c3d14b96d/JCMM-26-5493-g002.jpg

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