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弓形虫慢性感染以性别依赖的方式下调多个脑区中miR-132的表达。

Chronic infection of Toxoplasma gondii downregulates miR-132 expression in multiple brain regions in a sex-dependent manner.

作者信息

Li Y E, Kannan Geetha, Pletnikov Mikhail V, Yolken Robert H, Xiao Jianchun

机构信息

Stanley Division of Developmental Neurovirology,Department of Pediatrics,Johns Hopkins School of Medicine,Baltimore,Maryland 21287,USA.

Division of Neurobiology,Department of Psychiatry,Johns Hopkins School of Medicine,Baltimore,Maryland 21287,USA.

出版信息

Parasitology. 2015 Apr;142(4):623-32. doi: 10.1017/S003118201400167X. Epub 2014 Oct 29.

Abstract

MicroRNA-132 (miR-132) has been demonstrated to affect multiple neuronal functions and its dysregulation is linked to several neurological disorders. We previously showed that acute Toxoplasma gondii infection induces miR-132 expression both in vitro and in vivo. To investigate the impact of chronic infection on miR-132, we infected mice with T. gondii PRU strain and performed assessment 5 months later in six brain regions (cortex, hypothalamus, striatum, cerebellum, olfactory bulb and hippocampus) by qPCR. We found that while acute infection of T. gondii increases the expression of miR-132, chronic infection has the opposite effect. The effect varied amongst different regions of the brain and presented in a sex-dependent manner, with females exhibiting more susceptibility than males. MiR-132 and brain-derived neurotrophic factor (BDNF, an inducer of miR-132) were not co-varies in the brain areas of infected mice. T. gondii DNA/RNA was found in all tested brain regions and a selective tropism towards the hippocampus, based on bradyzoite density, was observed in both males and females. However, the expressions of miR-132 or BDNF were poorly reflected by the density of T. gondii in brain areas. Our findings highlight the importance of investigating the miR-132-mediated neuronal function in mice infected with T. gondii.

摘要

微小RNA-132(miR-132)已被证明可影响多种神经元功能,其失调与多种神经疾病有关。我们之前表明,急性弓形虫感染在体外和体内均可诱导miR-132表达。为了研究慢性感染对miR-132的影响,我们用弓形虫PRU株感染小鼠,并在5个月后通过qPCR对六个脑区(皮质、下丘脑、纹状体、小脑、嗅球和海马体)进行评估。我们发现,虽然急性弓形虫感染会增加miR-132的表达,但慢性感染却产生相反的效果。这种影响在大脑的不同区域有所不同,并且呈现出性别依赖性,雌性比雄性表现出更高的易感性。在受感染小鼠的脑区中,miR-132和脑源性神经营养因子(BDNF,miR-132的诱导剂)并不协同变化。在所有测试的脑区中均发现了弓形虫DNA/RNA,并且基于缓殖子密度观察到,雄性和雌性小鼠对海马体均具有选择性嗜性。然而,脑区中弓形虫的密度并不能很好地反映miR-132或BDNF的表达。我们的研究结果突出了在感染弓形虫的小鼠中研究miR-132介导的神经元功能的重要性。

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