Zika Virus Infection Alters the Circadian Clock Expression in Human Neuronal Monolayer and Neurosphere Cultures.

IF 3.6 4区 医学 Q3 CELL BIOLOGY
Thaíse Yasmine Vasconcelos de Lima Cavalcanti, Morganna Costa Lima, Paula Bargi-Souza, Rafael Freitas Oliveira Franca, Rodrigo Antonio Peliciari-Garcia
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引用次数: 0

Abstract

Rhythmic regulations are virtually described in all physiological processes, including central nervous system development and immunologic responses. Zika virus (ZIKV), a neurotropic arbovirus, has been recently linked to a series of birth defects and neurodevelopmental disorders. Given the well-characterized role of the intrinsic cellular circadian clock within neurogenesis, cellular metabolism, migration, and differentiation among other processes, this study aimed to characterize the influence of ZIKV infection in the circadian clock expression in human neuronal cells. For this, in vitro models of human-induced neuroprogenitor cells (hiNPCs) and neuroblastoma cell line SH-SY5Y, cultured as monolayer and neurospheres, were infected by ZIKV, followed by RNA-Seq and RT-qPCR investigation, respectively. Targeted circadian clock components presented mRNA oscillations only after exogenous synchronizing stimuli (Forskolin) in SH-SY5Y monolayer culture. Interestingly, when these cells were grown as 3D-arranged neurospheres, an intrinsic oscillatory expression pattern was observed for some core clock components without any exogenous stimulation. The ZIKV infection significantly disturbed the mRNA expression pattern of core clock components in both neuroblastoma cell culture models, which was also observed in hiNPCs infected with different strains of ZIKV. The ZIKV-mediated desynchronization of the circadian clock expression in human cells might further contribute to the virus impairment of neuronal metabolism and function observed in adults and ZIKV-induced congenital syndrome. In vitro models of Zika virus (ZIKV) neuronal infection. Human neuroprogenitor cells were cultured as monolayer and neurospheres and infected by ZIKV. Monolayer-cultured cells received forskolin (FSK) as a coupling factor for the circadian clock rhythmicity, while 3D-arranged neurospheres showed an intrinsic oscillatory pattern in the circadian clock expression. The ZIKV infection affected the mRNA expression pattern of core clock components in both cell culture models. The ZIKV-mediated desynchronization of the circadian clock machinery might contribute to the impairment of neuronal metabolism and function observed in both adults (e.g., Guillain-Barré syndrome) and ZIKV-induced congenital syndrome (microcephaly). The graphical abstract has been created with Canva at the canva.com website.

Abstract Image

寨卡病毒感染改变人类神经元单层和神经球培养物的昼夜节律钟表达
在所有生理过程中,包括中枢神经系统发育和免疫反应,几乎都有节奏性调节的描述。寨卡病毒(ZIKV)是一种侵袭神经的虫媒病毒,最近与一系列先天缺陷和神经发育障碍有关。鉴于细胞内在昼夜节律钟在神经发生、细胞新陈代谢、迁移和分化等过程中的作用已被充分描述,本研究旨在描述寨卡病毒感染对人类神经细胞昼夜节律钟表达的影响。为此,ZIKV 感染了体外培养的人类诱导神经祖细胞(hiNPCs)和神经母细胞瘤细胞系 SH-SY5Y(单层培养和神经球培养),然后分别进行了 RNA-Seq 和 RT-qPCR 研究。在SH-SY5Y单层培养中,只有在外源性同步刺激(佛司可林)后,靶向昼夜节律钟成分才会出现mRNA振荡。有趣的是,当这些细胞培养成三维排列的神经球时,在没有任何外源刺激的情况下也能观察到一些核心时钟成分的内在振荡表达模式。在这两种神经母细胞瘤细胞培养模型中,ZIKV 感染都明显干扰了核心时钟成分的 mRNA 表达模式,在感染了不同株 ZIKV 的 hiNPCs 中也观察到了这种情况。ZIKV 介导的人体细胞昼夜节律钟表达不同步可能进一步导致在成人中观察到的病毒对神经元代谢和功能的损害以及 ZIKV 引起的先天性综合征。寨卡病毒(ZIKV)神经元感染的体外模型。将人类神经祖细胞培养成单层细胞和神经球,并用 ZIKV 感染。单层培养的细胞接受福斯可林(FSK)作为昼夜节律钟节律的耦合因子,而三维排列的神经球则显示出昼夜节律钟表达的内在振荡模式。ZIKV感染影响了两种细胞培养模型中核心时钟成分的mRNA表达模式。ZIKV介导的昼夜节律时钟机制不同步可能是成人(如格林-巴利综合征)和ZIKV诱导的先天综合征(小头畸形)中观察到的神经元代谢和功能受损的原因。该图表摘要是在 canva.com 网站上使用 Canva 制作的。
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来源期刊
CiteScore
7.70
自引率
0.00%
发文量
137
审稿时长
4-8 weeks
期刊介绍: Cellular and Molecular Neurobiology publishes original research concerned with the analysis of neuronal and brain function at the cellular and subcellular levels. The journal offers timely, peer-reviewed articles that describe anatomic, genetic, physiologic, pharmacologic, and biochemical approaches to the study of neuronal function and the analysis of elementary mechanisms. Studies are presented on isolated mammalian tissues and intact animals, with investigations aimed at the molecular mechanisms or neuronal responses at the level of single cells. Cellular and Molecular Neurobiology also presents studies of the effects of neurons on other organ systems, such as analysis of the electrical or biochemical response to neurotransmitters or neurohormones on smooth muscle or gland cells.
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