Assessing Rat Forelimb and Hindlimb Motor Unit Connectivity as Objective and Robust Biomarkers of Spinal Motor Neuron Function.
Assessing Rat Forelimb and Hindlimb Motor Unit Connectivity as Objective and Robust Biomarkers of Spinal Motor Neuron Function.
复制标题
评估大鼠前肢和后肢运动单位连接性作为脊髓运动神经元功能的客观和稳健的生物标志物。
DOI：
10.1038/s41598-019-53235-w
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发表时间：
2019
影响因子：
4.6
通讯作者：
Arnold,WDavid
中科院分区：
文献类型：
--
作者：
Harrigan,MarkusE;Filous,AngelaR;Tosolini,AndrewP;Morris,Renee;Schwab,JanM;Arnold,WDavid
Sensitive and objective biomarkers of neuronal injury, degeneration, and regeneration can help facilitate translation of experimental findings into clinical testing. Whereas measures of upper motor neuron connectivity have been readily established, functional assessments of lower motor neuron (LMN) innervation of forelimb muscles are lacking. Compound muscle action potential (CMAP) and motor unit (MU) number estimation (MUNE) are well-established methods that allow longitudinal MU integrity monitoring in patients. In analogy we refined CMAP and MUNE methods for assessing spinal MU input in the rat forelimb and hindlimb. Repeated CMAP and MUNE recordings are robust (coefficients of variability: 4.5–11.3%), and MUNE measurements from forelimb wrist flexor muscles (415 ± 8 [SEM]) align with back-traced anatomical LMN counts (336 ± 16 [SEM]). For disease validation, cross-sectional blinded electrophysiological and muscle contractility measurements were obtained in a cohort of G93A SOD1 mutant overexpressing rats and compared with controls. Longitudinal assessment of mutant animals demonstrated progressive motor unit decline in the hindlimb to a greater extent than the forelimb. Hindlimb CMAP and MUNE demonstrated strong correlations with plantarflexion muscle contractility. Cross-species assessment of upper/fore- limb and lower/hind- limb motor units using objective electrophysiological CMAP and MUNE values as biomarkers will guide and improve bi-directional translation.
