Nold Andreas, Batulin Danylo, Birkner Katharina, Bittner Stefan, Tchumatchenko Tatjana
Theory of Neural Dynamics, Max Planck Institute for Brain Research, 60438 Frankfurt am Main, Germany.
Frankfurt Institute for Advanced Studies (FIAS), 60438 Frankfurt am Main, Germany.
iScience. 2020 Oct 22;23(11):101701. doi: 10.1016/j.isci.2020.101701. eCollection 2020 Nov 20.
Glia, the helper cells of the brain, are essential in maintaining neural resilience across time and varying challenges: By reacting to changes in neuronal health glia carefully balance repair or disposal of injured neurons. Malfunction of these interactions is implicated in many neurodegenerative diseases. We present a reductionist model that mimics repair-or-dispose decisions to generate a hypothesis for the cause of disease onset. The model assumes four tissue states: healthy and challenged tissue, primed tissue at risk of acute damage propagation, and chronic neurodegeneration. We discuss analogies to progression stages observed in the most common neurodegenerative conditions and to experimental observations of cellular signaling pathways of glia-neuron crosstalk. The model suggests that the onset of neurodegeneration can result as a compromise between two conflicting goals: short-term resilience to stressors versus long-term prevention of tissue damage.
神经胶质细胞作为大脑的辅助细胞，对于在不同时间和各种挑战下维持神经弹性至关重要：通过对神经元健康变化做出反应，神经胶质细胞谨慎地平衡受损神经元的修复或清除。这些相互作用的功能失调与许多神经退行性疾病有关。我们提出了一个简化模型，该模型模拟修复或清除决策，以生成疾病发病原因的假设。该模型假设了四种组织状态：健康组织和受挑战组织、有急性损伤传播风险的预激组织以及慢性神经退行性变组织。我们讨论了与在最常见的神经退行性疾病中观察到的进展阶段以及神经胶质细胞与神经元相互作用的细胞信号通路的实验观察结果的类比。该模型表明，神经退行性变的发生可能是两个相互冲突的目标之间妥协的结果：对应激源的短期弹性与对组织损伤的长期预防。
