Unique molecular features and cellular responses differentiate two populations of motor cortical layer 5b neurons in a preclinical model of ALS.
Unique molecular features and cellular responses differentiate two populations of motor cortical layer 5b neurons in a preclinical model of ALS.
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DOI：
10.1016/j.celrep.2022.110556
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发表时间：
2022-03-22
期刊：
影响因子：
8.8
通讯作者：
Schmidt, Eric F.
中科院分区：
文献类型：
--
作者：
Moya, Maria, V;Kim, Rachel D.;Rao, Meghana N.;Cotto, Bianca A.;Pickett, Sarah B.;Sferrazza, Caroline E.;Heintz, Nathaniel;Schmidt, Eric F.
许多神经退行性疾病，如肌萎缩性侧索硬化症（ALS），导致中枢神经系统中离散细胞类型的选择性变性，尽管许多与疾病相关的基因普遍表达。治疗的进步取决于理解在致病突变的背景下脆弱细胞病理基础上的独特细胞适应。在这里，我们使用bacTRAP分子谱来阐明临床前ALS模型中皮质上运动神经元的细胞类型特异性分子反应。利用标记运动皮层中不同的脆弱或弹性投射神经元群的两种bacTRAP小鼠系，我们发现氧化磷酸化（Oxphos）途径的调节是两种细胞类型的共同反应。然而，Oxphos相关基因的基线表达和活性氧处理的差异可能导致易感细胞的选择性变性。这些结果为识别神经退行性疾病中细胞类型特异性过程提供了一个框架。Moya等人使用bacTRAP小鼠品系来表征SOD1-G93A ALS小鼠模型中运动皮层5b层投射神经元的两个高度相关的亚群，它们对神经退行性变具有不同的易感性。他们确定了参与生物能量学的基因调控是调节易感性的关键因素。
Many neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), lead to the selective degeneration of discrete cell types in the CNS despite the ubiquitous expression of many genes linked to disease. Therapeutic advancement depends on understanding the unique cellular adaptations that underlie pathology of vulnerable cells in the context of disease-causing mutations. Here, we employ bacTRAP molecular profiling to elucidate cell type-specific molecular responses of cortical upper motor neurons in a preclinical ALS model. Using two bacTRAP mouse lines that label distinct vulnerable or resilient projection neuron populations in motor cortex, we show that the regulation of oxidative phosphorylation (Oxphos) pathways is a common response in both cell types. However, differences in the baseline expression of genes involved in Oxphos and the handling of reactive oxygen species likely lead to the selective degeneration of the vulnerable cells. These results provide a framework to identify cell-type-specific processes in neurodegenerative disease. Moya et al. use bacTRAP mouse lines to characterize two highly related subpopulations of layer 5b projection neurons in motor cortex that are differentially susceptible to neurodegeneration in the SOD1-G93A mouse model of ALS. They identify the regulation of genes involved in bioenergetics as a key factor regulating susceptibility.
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影响因子：
6.1
作者：
Evans CS;Holzbaur ELF
通讯作者：
Holzbaur ELF
DOI：
10.1126/science.1201940
发表时间：
2011-08-26
期刊：
Science (New York, N.Y.)
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影响因子：
9.9
作者：
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通讯作者：
Stewart, H