Horai Tadasu, Boku Shuken, Okazaki Satoshi, Otsuka Ikuo, Ratta-Apha Woraphat, Mouri Kentaro, Yamaki Naruhisa, Hirata Takashi, Hishimoto Akitoyo
Department of Psychiatry, Kobe University Graduate School of Medicine, Kobe, Japan.
Department of Psychiatry, Kobe University Graduate School of Medicine, Kobe, Japan; Department of Neuropsychiatry, Kumamoto University Faculty of Life Sciences, Kumamoto, Japan.
J Psychiatr Res. 2020 Dec;131:102-107. doi: 10.1016/j.jpsychires.2020.09.006. Epub 2020 Sep 11.
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.
微小RNA（miRNA）已在包括精神分裂症（SZ）在内的神经发育和精神疾病中得到研究。先前的研究表明，SZ患者的死后脑组织和外周血中存在miRNA失调。这些表明miRNA可能在SZ的病理生理学中起作用，并可能是SZ的潜在生物标志物。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，在成年海马神经祖细胞（NPC）中富集的miR-19a和19b在源自SZ患者诱导多能干细胞的人NPC中增加。然而，尚不清楚SZ患者外周血中miR-19a和19b的水平是否改变，以及miR-19a和19b如何影响神经发生。为了阐明这些问题，首先我们用定量RT-PCR检测了SZ患者外周血中miR-19a和19b的水平，结果显示SZ患者（N = 22）外周血中miR-19b的水平显著高于健康对照（N = 19）（miR-19a：p = 0.5733，miR-19b：p = 0.0038），而miR-19a的水平无显著差异。接下来，我们用BrdU检测法和TUNEL检测法研究了miR-19b对新生小鼠海马来源NPC增殖和存活的影响。miR-19b的沉默显著增加了新生小鼠海马来源NPC的增殖（N = 5，p = 0.0139），但对其存活无显著影响（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，并且较高水平的miR-19b可能通过减弱海马NPC的增殖增加SZ的易感性。
