Sun Xiahui, Wang Ting, Wang Yongliang, Ai Kang, Pan Ge, Li Yan, Zhou Chunxue, He Shenyi, Cong Hua
Department of Pathogenic Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
College of Animal Science and Technology, Jilin Agricultural University, Changchun, China.
Front Mol Neurosci. 2020 May 15;13:77. doi: 10.3389/fnmol.2020.00077. eCollection 2020.
Though it is well known that chronic infections of () can induce mental and behavioral disorders in the host, little is known about the role of long non-coding RNAs (lncRNAs) in this pathological process. In this study, we employed an advanced lncRNAs and mRNAs integration chip (Affymetrix HTA 2.0) to detect the expression of both lncRNAs and mRNAs in Chinese 1 strain infected mouse brain. As a result, for the first time, the downregulation of lncRNA-11496 (NONMMUGO11496) was identified as the responsible factor for this pathological process. We showed that dysregulation of lncRNA-11496 affected proliferation, differentiation and apoptosis of mouse microglia. Furthermore, we proved that Mef2c (Myocyte-specific enhancer factor 2C), a member of the MEF2 subfamily, is the target gene of lncRNA-11496. In a more detailed study, we confirmed that lncRNA-11496 positively regulated the expression of Mef2c by binding to histone deacetylase 2 (HDAC2). Importantly, Mef2c itself could coordinate neuronal differentiation, survival, as well as synapse formation. Thus, our current study provides the first evidence in terms of the modulatory action of lncRNAs in chronic toxoplasmosis in infected mouse brain, providing a solid scientific basis for using lncRNA-11496 as a therapeutic target to treat induced neurological disorder.
尽管众所周知,()的慢性感染可诱导宿主出现精神和行为障碍,但关于长链非编码RNA(lncRNA)在这一病理过程中的作用却知之甚少。在本研究中,我们采用先进的lncRNA和mRNA整合芯片(Affymetrix HTA 2.0)来检测中国1株感染小鼠脑内lncRNA和mRNA的表达。结果,首次确定lncRNA - 11496(NONMMUGO11496)的下调是这一病理过程的致病因素。我们发现lncRNA - 11496的失调影响了小鼠小胶质细胞的增殖、分化和凋亡。此外,我们证明MEF2亚家族成员Mef2c(肌细胞特异性增强因子2C)是lncRNA - 11496的靶基因。在更详细的研究中,我们证实lncRNA - 11496通过与组蛋白去乙酰化酶2(HDAC2)结合来正向调节Mef2c的表达。重要的是,Mef2c本身可以协调神经元的分化、存活以及突触形成。因此,我们目前的研究首次提供了lncRNA在感染小鼠脑内慢性弓形虫病中的调节作用的证据,为将lncRNA - 11496用作治疗由()诱导的神经障碍的治疗靶点提供了坚实的科学依据。