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miR-19b is elevated in peripheral blood of schizophrenic patients and attenuates proliferation of hippocampal neural progenitor cells.
Journal of Psychiatric Research ( IF 3.7 ) Pub Date : 2020-09-11 , DOI: 10.1016/j.jpsychires.2020.09.006
Tadasu Horai 1 , Shuken Boku 2 , Satoshi Okazaki 1 , Ikuo Otsuka 1 , Woraphat Ratta-Apha 3 , Kentaro Mouri 1 , Naruhisa Yamaki 1 , Takashi Hirata 1 , Akitoyo Hishimoto 4
Affiliation  

MicroRNAs (miRNAs) have been investigated in neurodevelopmental and psychiatric disorders including schizophrenia (SZ). Previous studies showed miRNAs dysregulation in postmortem brain tissues and peripheral blood of SZ patients. These suggest that miRNAs may play a role in the pathophysiology of SZ and be a potential biomarker of SZ. Previous studies also showed that miRNAs regulated neurogenesis and that neurogenesis was involved in the pathophysiology of SZ. In addition, a recent study showed that miR-19a and 19b, enriched in neural progenitor cells (NPC) in adult hippocampus, were increased in human NPC derived from induced pluripotent stem cell derived from SZ patients. However, it remains unclear whether the levels of miR-19a and 19b are altered in peripheral blood of SZ patients and how miR-19a and 19b affects neurogenesis. To elucidate them, first we examined the levels of miR-19a and 19b in peripheral blood of SZ patients with quantitative RT-PCR and showed that the level of miR-19b, but not miR-19a, was significantly higher (miR-19a: p = 0.5733, miR-19b: p = 0.0038) in peripheral blood of SZ patients (N = 22) than that of healthy controls (N = 19). Next, we examined the involvement of miR-19b in proliferation and survival of mouse neonatal mice hippocampus-derived NPC with BrdU assay and TUNEL assay. The silencing of miR-19b significantly increased proliferation (N = 5, p = 0.0139), but not survival (N = 5, p = 0.9571), of neonatal mice hippocampus-derived NPC. These results suggest that the level of miR-19b in peripheral blood is a potential biomarker of schizophrenia and that the higher level of miR-19b may increase the vulnerability of SZ via attenuating proliferation of hippocampal NPC.



中文翻译:

miR-19b 在精神分裂症患者的外周血中升高并减弱海马神经祖细胞的增殖。

MicroRNAs (miRNAs) 已在包括精神分裂症 (SZ) 在内的神经发育和精神疾病中进行了研究。先前的研究表明,SZ 患者死后脑组织和外周血中的 miRNA 失调。这些表明 miRNA 可能在 SZ 的病理生理学中发挥作用,并可能成为 SZ 的生物标志物。先前的研究还表明,miRNA 调节神经发生,并且神经发生参与了 SZ 的病理生理学。此外,最近的一项研究表明,在源自 SZ 患者的诱导多能干细胞的人类 NPC 中,富含成人海马神经祖细胞 (NPC) 的 miR-19a 和 19b 增加。然而,尚不清楚 SZ 患者外周血中 miR-19a 和 19b 的水平是否发生改变,以及 miR-19a 和 19b 如何影响神经发生。 SZ 患者(N = 22)外周血中的p  = 0.5733,miR-19b:p = 0.0038)比健康对照组(N = 19)。接下来,我们用BrdU测定和TUNEL测定检查了miR-19b在小鼠新生小鼠海马衍生的NPC的增殖和存活中的参与。 miR-19b 的沉默显着增加了新生小鼠海马衍生 NPC 的增殖(N = 5,p  = 0.0139),但不增加存活率(N = 5,p = 0.9571)。这些结果表明,外周血中 miR-19b 的水平是精神分裂症的潜在生物标志物,较高水平的 miR-19b 可能通过减弱海马 NPC 的增殖而增加 SZ 的易感性。

更新日期:2020-09-18
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