Atlanta VA Center for Visual and Neurocognitive Rehabilitation, Decatur, Georgia, USA.
Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA.
J Neurosci Res. 2022 Sep;100(9):1695-1706. doi: 10.1002/jnr.25063. Epub 2022 May 18.
Exercise is an effective neuroprotective intervention that preserves retinal function and structure in several animal models of retinal degeneration. However, the retinal cell types governing exercise-induced neuroprotection remain elusive. Previously, we found exercise-induced retinal neuroprotection was associated with increased levels of retinal brain-derived neurotrophic factor (BDNF) and required intact signal transduction with its high-affinity receptor, tropomyosin kinase B (TrkB). Brain studies have shown astrocytes express BDNF and TrkB and that decreased BDNF-TrkB signaling in astrocytes contributes to neurodegeneration. Additionally, exercise has been shown to alter astrocyte morphology. Using a light-induced retinal degeneration (LIRD) model, we investigated how exercise influences retinal astrocytes in adult male BALB/c mice. Treadmill exercise in dim control and LIRD groups had increased astrocyte density, GFAP labeling, branching, dendritic endpoints, and arborization. Meanwhile, inactive LIRD animals had significant reductions in all measured parameters. Additionally, exercised groups had increased astrocytic BDNF expression that was visualized using proximity ligase assay. Isolated retinal astrocytes from exercised LIRD groups had significantly increased expression of a specific isoform of TrkB associated with cell survival, TrkB.FL. Conversely, inactive LIRD isolated retinal astrocytes had significantly increased expression of TrkB.T1, which has been implicated in neuronal cell death. Our data indicate exercise not only alters retinal astrocyte morphology but also promotes specific BDNF-TrkB signaling associated with cell survival and protection during retinal degeneration. These findings provide novel insights into the effects of treadmill exercise on retinal astrocyte morphology and cellular expression, highlighting retinal astrocytes as a potential cell type involved in BDNF-TrkB signaling.
运动是一种有效的神经保护干预措施，可以在几种视网膜变性的动物模型中保护视网膜功能和结构。然而，控制运动诱导的神经保护的视网膜细胞类型仍不清楚。先前，我们发现运动诱导的视网膜神经保护与视网膜脑源性神经营养因子 (BDNF) 水平升高有关，并且需要其高亲和力受体原肌球蛋白激酶 B (TrkB) 的完整信号转导。脑研究表明，星形胶质细胞表达 BDNF 和 TrkB，星形胶质细胞中 BDNF-TrkB 信号的减少导致神经退行性变。此外，运动已被证明可以改变星形胶质细胞的形态。我们使用光诱导的视网膜变性 (LIRD) 模型，研究了运动如何影响成年雄性 BALB/c 小鼠的视网膜星形胶质细胞。在昏暗对照和 LIRD 组中，跑步机运动增加了星形胶质细胞密度、GFAP 标记、分支、树突末端和分支。同时，不活跃的 LIRD 动物所有测量参数均显著降低。此外，运动组的星形胶质细胞 BDNF 表达增加，使用邻近连接测定法可观察到这一点。来自运动 LIRD 组的分离的视网膜星形胶质细胞显著增加了与细胞存活相关的特定 TrkB 同工型 TrkB.FL 的表达。相反，不活跃的 LIRD 分离的视网膜星形胶质细胞中 TrkB.T1 的表达显著增加，TrkB.T1 已被牵连到神经元细胞死亡中。我们的数据表明，运动不仅改变了视网膜星形胶质细胞的形态，还促进了特定的 BDNF-TrkB 信号转导，与视网膜变性过程中的细胞存活和保护有关。这些发现为跑步机运动对视网膜星形胶质细胞形态和细胞表达的影响提供了新的见解，突出了视网膜星形胶质细胞作为涉及 BDNF-TrkB 信号转导的潜在细胞类型。
