PDF(Pubmed)
Abstract：
Amyotrophic lateral sclerosis (ALS) is characterized by the progressive loss of somatic motor neurons. A major focus has been directed to motor neuron intrinsic properties as a cause for degeneration, while less attention has been given to the contribution of spinal interneurons. In the present work, we applied multiplexing detection of transcripts and machine learning-based image analysis to investigate the fate of multiple spinal interneuron populations during ALS progression in the SOD1G93A mouse model. The analysis showed that spinal inhibitory interneurons are affected early in the disease, before motor neuron death, and are characterized by a slow progressive degeneration, while excitatory interneurons are affected later with a steep progression. Moreover, we report differential vulnerability within inhibitory and excitatory subpopulations. Our study reveals a strong interneuron involvement in ALS development with interneuron specific degeneration. These observations point to differential involvement of diverse spinal neuronal circuits that eventually may be determining motor neuron degeneration.
摘要：
肌萎缩侧索硬化(ALS)的特征在于躯体运动神经元的进行性丧失。一个主要的焦点是运动神经元的内在特性，作为退化的原因，虽然对脊髓中间神经元的贡献关注较少。在目前的工作中,我们在SOD1G93A小鼠模型中应用了转录本的多重检测和基于机器学习的图像分析来研究ALS进展过程中多个脊髓中间神经元群体的命运.分析表明，脊髓抑制性中间神经元在疾病早期受到影响，在运动神经元死亡之前，以缓慢进行性退化为特征，而兴奋性中间神经元后来受到影响，进展迅速。此外，我们报告了抑制性和兴奋性亚群中的差异脆弱性。我们的研究揭示了中间神经元特异性变性与ALS发育的强烈参与。这些观察结果指出，最终可能决定运动神经元变性的各种脊髓神经元回路的不同参与。
