Key Laboratory of Ethnomedicine of Ministry of Education, Center on Translational Neuroscience, School of Pharmacy, Minzu University of China, Beijing, China.
College of Life and Environmental Sciences, Minzu University of China, Beijing, China.
Schizophr Bull. 2021 Aug 21;47(5):1288-1299. doi: 10.1093/schbul/sbab039.
Exosomes are involved in the pathophysiology of neuropsychiatric diseases, but the role of exosomes in schizophrenia (SCZ) is unclear. Here, we demonstrate that transplantation of serum exosomes from SCZ patients into mice caused behavioral abnormalities such as deficits in prepulse inhibition and sociability, hyperactivity, and anxiogenesis. A comparative bioinformatics analysis suggested shared and distinct differentially expressed genes (DEGs) and enriched molecular pathways in the brains of SCZ exosome-recipient mice, methylazoxymethanol acetate-treated rats, and SCZ patients, which correlates evidence of altered prefrontal-hippocampal functional coherence in SCZ. A large proportion of SCZ-relevant DEGs in the exosome-recipient mice were targets of DE exosomal miRNAs in SCZ patients. Furthermore, we identified 20 hub genes for SCZ risk genes, including BDNF and NRG1, which were DE miRNA targets in SCZ. Collectively, our study suggests that SCZ exosome transplantation caused SCZ-relevant behaviors in mice, and epigenetic regulation may contribute to the phenotypes in the SCZ exosome-recipient mice. Our results may provide a potential animal model and novel therapeutic targets for SCZ.
外泌体参与神经精神疾病的病理生理学，但外泌体在精神分裂症（SCZ）中的作用尚不清楚。在这里，我们证明来自 SCZ 患者的血清外泌体移植到小鼠中会引起行为异常，如前脉冲抑制和社交能力下降、多动和焦虑症。比较生物信息学分析表明，SCZ 外泌体受赠小鼠、醋酸甲基氧化偶氮甲醇处理大鼠和 SCZ 患者的大脑中存在共享和独特的差异表达基因（DEG）和丰富的分子途径，这与 SCZ 中前额叶-海马功能连贯性改变的证据相关。外泌体受赠小鼠中的大量 SCZ 相关 DEG 是 SCZ 患者外泌体中差异表达 miRNA 的靶标。此外，我们确定了 20 个 SCZ 风险基因的枢纽基因，包括 BDNF 和 NRG1，它们是 SCZ 中差异表达 miRNA 的靶标。综上所述，我们的研究表明，SCZ 外泌体移植导致小鼠出现 SCZ 相关行为，表观遗传调控可能导致 SCZ 外泌体受赠小鼠的表型。我们的结果可能为 SCZ 提供一种潜在的动物模型和新的治疗靶点。
