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Assessing Rat Forelimb and Hindlimb Motor Unit Connectivity as Objective and Robust Biomarkers of Spinal Motor Neuron Function

Harrigan, M; Filous, A; Tosolini, A; Morris, R; Schwab, J; Arnold, WD; (2019) Assessing Rat Forelimb and Hindlimb Motor Unit Connectivity as Objective and Robust Biomarkers of Spinal Motor Neuron Function. Scientific Reports , 9 , Article 16699. 10.1038/s41598-019-53235-w. Green open access

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Abstract

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.

Type: Article
Title: Assessing Rat Forelimb and Hindlimb Motor Unit Connectivity as Objective and Robust Biomarkers of Spinal Motor Neuron Function
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41598-019-53235-w
Publisher version: https://doi.org/10.1038/s41598-019-53235-w
Language: English
Additional information: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Keywords: Diseases of the nervous system; Electromyography – EMG; Motor neuron disease; Peripheral nervous system; Spinal cord diseases
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/10084599
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