Glial cells modulate retinal cell survival in rotenone-induced neural degeneration.
Glial cells modulate retinal cell survival in rotenone-induced neural degeneration.
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DOI：
10.1038/s41598-021-90604-w
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发表时间：
2021-05-27
影响因子：
4.6
通讯作者：
Nakazawa T
中科院分区：
文献类型：
--
作者：
Tawarayama H;Inoue-Yanagimachi M;Himori N;Nakazawa T
线粒体复合物I抑制剂鱼藤酮的管理提供了一个很好的模型来研究氧化应激相关的神经退行性疾病的病理机制。在这项研究中，我们研究了在鱼藤酮诱导的氧化应激条件下，神经胶质细胞在视网膜细胞存活和变性中的作用。将小鼠源性Müller、小胶质细胞（BV-2）和分离的视网膜细胞用于体外实验。基因表达水平和细胞活力分别采用定量逆转录-聚合酶链反应和alamarBlue测定法测定。通过用鱼藤酮刺激神经胶质细胞来制备条件培养基。视网膜神经节细胞（RGC）和内核层（INL）分别通过免疫组织化学和伊红/苏木精在大鼠视网膜切片上可视化。鱼藤酮剂量依赖性地诱导胶质细胞死亡。用鱼藤酮或鱼藤酮刺激的神经胶质细胞条件培养基治疗改变了神经胶质细胞中生长因子和炎性细胞因子的基因表达。在鱼藤酮刺激的或Müller细胞条件培养基刺激的BV-2细胞的条件培养基中培养后，分离的视网膜细胞的活力显著增加。此外，玻璃体内注射神经营养素-5预防鱼藤酮诱导的大鼠RGC数量和INL厚度的减少。因此，神经胶质细胞通过改变生长因子的表达，特别是小胶质细胞衍生的Ntf 5和促炎细胞因子的上调，对鱼藤酮诱导的神经变性中的视网膜细胞存活产生积极和消极的影响。
Administration of the mitochondrial complex I inhibitor rotenone provides an excellent model to study the pathomechanism of oxidative stress-related neural degeneration diseases. In this study, we examined the glial roles in retinal cell survival and degeneration under the rotenone-induced oxidative stress condition. Mouse-derived Müller, microglial (BV-2), and dissociated retinal cells were used for in vitro experiments. Gene expression levels and cell viability were determined using quantitative reverse transcription-polymerase chain reaction and the alamarBlue assay, respectively. Conditioned media were prepared by stimulating glial cells with rotenone. Retinal ganglion cells (RGCs) and inner nuclear layer (INL) were visualized on rat retinal sections by immunohistochemistry and eosin/hematoxylin, respectively. Rotenone dose-dependently induced glial cell death. Treatment with rotenone or rotenone-stimulated glial cell-conditioned media altered gene expression of growth factors and inflammatory cytokines in glial cells. The viability of dissociated retinal cells significantly increased upon culturing in media conditioned with rotenone-stimulated or Müller cell-conditioned media-stimulated BV-2 cells. Furthermore, intravitreal neurotrophin-5 administration prevented the rotenone-induced reduction of RGC number and INL thickness in rats. Thus, glial cells exerted both positive and negative effects on retinal cell survival in rotenone-induced neural degeneration via altered expression of growth factors, especially upregulation of microglia-derived Ntf5, and proinflammatory cytokines.
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影响因子：
16.2
作者：
IP, NY;STITT, TN;YANCOPOULOS, GD
通讯作者：
YANCOPOULOS, GD
四甲基吡嗪通过 TLR4/NF-kappa B 信号通路抑制小胶质细胞活化，减轻内毒素诱导的视网膜炎症
影响因子：
7.5
作者：
Han, Xiaokun;Chen, Xi;Yu, Keming
通讯作者：
Yu, Keming
影响因子：
5.3
作者：
Fleming, SM;Zhu, CN;Chesselet, MF
通讯作者：
Chesselet, MF
影响因子：
1.7
作者：
CUI, Q;HARVEY, AR
通讯作者：
HARVEY, AR
影响因子：
6.2
作者：
Fischer, Andy J.;Zelinka, Christopher;Milani-Nejad, Nima
通讯作者：
Milani-Nejad, Nima