Nippostrongylus brasiliensis infection inhibits hippocampal neurogenesis in mice

Nippostrongylus brasiliensis infection inhibits hippocampal neurogenesis in mice
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DOI:
10.1111/neup.12596
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发表时间:
2019-09
期刊:
影响因子:
2.3
通讯作者:
M. Sakurai;Junya Kurachi;Y. Sakai;M. Morimoto
M. Sakurai;Junya Kurachi;Y. Sakai;M. Morimoto
中科院分区:
医学4区
文献类型:
--
作者:
M. Sakurai;Junya Kurachi;Y. Sakai;M. Morimoto

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长期以来,大脑一直被认为是“免疫特权”的场所;然而,最近的证据表明,在生理和病理条件下存在脑免疫相互作用。神经发生是一个产生功能整合的神经元的过程,发生在哺乳动物的成年大脑中。成年期的神经发生主要发生在海马齿状回颗粒下区(SGZ)和脑室下区(SVZ)。一些研究表明,免疫反应或改变可能会影响成人神经发生活动,这表明免疫系统和成人神经发生之间的联系。蠕虫感染是Th 2免疫应答的激活因子之一。然而,这种类型的免疫反应对成人神经发生的影响还没有得到很好的研究。在这项研究中,我们评估了成年神经发生在感染蠕虫Nippostrongylus brasiliensis(Nb)的小鼠。免疫组织化学显示,到感染后第9天,Nb感染小鼠的SGZ中双皮质素阳性细胞和双皮质素/5-溴脱氧尿苷(BrdU)双阳性细胞的数量均减少。然而,SGZ中BrdU阳性新生细胞的总数没有变化。在感染小鼠的SVZ中未检测到显著变化。此外,使用逆转录-定量聚合酶链反应,我们观察到海马中对神经发生重要的神经营养因子的表达水平没有显著变化。总之,我们的研究结果表明,成年神经发生在SGZ,但不是在SVZ,抑制Nb感染。Th 2免疫应答可能对海马神经发生有抑制作用。
The brain has long been considered a site of “immune privilege”; however, recent evidence indicates the presence of brain–immune interactions in physiological and pathological conditions. Neurogenesis, a process of generating functionally integrated neurons, occurs in the adult brain of mammals. The adult neurogenesis predominantly takes place in the subgranular zone (SGZ) of the hippocampal dentate gyrus and the subventricular zone (SVZ). Several studies have shown that an immune reaction or alteration could affect adult neurogenesis activity, suggesting a link between the immune system and adult neurogenesis. Helminth infection is one of the activators of Th2 immune response. However, the influence of this type of immune reaction on adult neurogenesis is not well studied. In this study, we evaluated adult neurogenesis in mice infected with the helminth Nippostrongylus brasiliensis (Nb). Immunohistochemically, the number of both doublecortin‐positive cells and doublecortin/5‐bromodeoxyuridine (BrdU)‐double‐positive cells was decreased in the SGZ of Nb‐infected mice by day 9 after infection. However, the total number of BrdU‐positive newborn cells in the SGZ did not change. In no significant alterations were detected in the SVZ of infected mice. In addition, using reverse transcription‐quantitative polymerase chain reaction, we observed no significant changes in the expression levels of neurotropic factors important for neurogenesis in the hippocampus. In conclusion, our results indicate that adult neurogenesis in SGZ, but not in SVZ, is inhibited by Nb infection. Th2 immune response might have a suppressive effect on hippocampal neurogenesis.