A Balancing Act: The Immune System Supports Neurodegeneration and Neurogenesis

A Balancing Act: The Immune System Supports Neurodegeneration and Neurogenesis
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DOI:
10.1007/s10571-020-00787-5
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发表时间:
2020-01-24
影响因子:
4
通讯作者:
Allodi, Silvana
Allodi, Silvana
中科院分区:
医学3区
文献类型:
--
作者:
Chaves da Silva, Paula Grazielle;Hsu, Kelly;Allodi, Silvana

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十足目甲壳类动物与哺乳动物一样,在一生中都保留着产生新神经元的能力。在哺乳动物中,免疫细胞与产生成年神经元的干细胞密切相关。在小龙虾中,有证据表明,源自免疫系统的免疫细胞(血细胞)进入神经源区域并转化为神经祖细胞。这种非传统的免疫活动在正常生理条件下持续发生,但在病理条件下(神经退行性变)却知之甚少。在这项研究中,研究了成年小龙虾神经变性(单侧触角消融)过程中的免疫系统及其与神经发生的关系。我们的实验表明,消融后(1)成年小龙虾大脑神经源性区域的增殖细胞减少; (2) 免疫反应,但不是神经发生,是消融侧依赖性的; (3)诱导型一氧化氮合酶(iNOS)在免疫反应过程中在含有神经祖细胞的神经源性微环境中发挥着至关重要的作用; (4) 触角投射所针对的脑部区域对病变作出急性反应(15分钟),增加局部免疫细胞的数量; (5) 免疫细胞被募集到同侧神经源性微环境周围的区域; (6)微环境中的脉管系统通过扩张以及可能的新血管形成来做出敏锐的反应。我们得出结论,免疫细胞在神经变性和神经发生中都很重要,在生理条件下有助于维持神经源性生态位(神经发生)中神经前体细胞的数量,而在病理条件下(神经变性)则通过协调与神经源性生态位相关的NO释放和血管反应。我们的数据表明,神经损伤和恢复参与了这些竞争性免疫细胞角色之间的平衡。
Decapod crustaceans, like mammals, retain the ability to make new neurons throughout life. In mammals, immune cells are closely associated with stem cells that generate adult-born neurons. In crayfish, evidence suggests that immune cells (hemocytes) originating in the immune system travel to neurogenic regions and transform into neural progenitor cells. This nontraditional immune activity takes place continuously under normal physiological conditions, but little is known under pathological conditions (neurodegeneration). In this study, the immune system and its relationship with neurogenesis were investigated during neurodegeneration (unilateral antennular ablation) in adult crayfish. Our experiments show that after ablation (1) Proliferating cells decrease in neurogenic areas of the adult crayfish brain; (2) The immune response, but not neurogenesis, is ablation-side dependent; (3) Inducible nitric oxide synthase (iNOS) plays a crucial role in the neurogenic niche containing neural progenitors during the immune response; (4) Brain areas targeted by antennular projections respond acutely (15 min) to the lesion, increasing the number of local immune cells; (5) Immune cells are recruited to the area surrounding the ipsilateral neurogenic niche; and (6) The vasculature in the niche responds acutely by dilation and possibly also neovascularization. We conclude that immune cells are important in both neurodegeneration and neurogenesis by contributing in physiological conditions to the maintenance of the number of neural precursor cells in the neurogenic niche (neurogenesis), and in pathological conditions (neurodegeneration) by coordinating NO release and vascular responses associated with the neurogenic niche. Our data suggest that neural damage and recovery participate in a balance between these competing immune cell roles.