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  4. 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

Scientific Reports, 2019 · DOI: 10.1038/s41598-019-53235-w · Published: November 18, 2019

PhysiologyNeurologyBioinformatics

Simple Explanation

This study refines methods to assess spinal motor unit input in rat limbs, using CMAP and MUNE. These methods are reliable and align with anatomical motor neuron counts. The study validates these methods in SOD1 mutant rats, which model ALS, showing progressive motor unit decline, particularly in the hindlimb. This decline correlates with muscle contractility. The research aims to improve cross-species translation by using electrophysiological values as biomarkers, which can guide and improve bi-directional translation between animal models and clinical applications.

Study Duration
20 days longitudinal assessment
Participants
Sprague Dawley rats (wild type and G93A SOD1 mutant overexpressing)
Evidence Level
Not specified

Key Findings

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    CMAP and MUNE recordings are robust with low coefficients of variability in both forelimb and hindlimb of rats.
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    MUNE measurements from forelimb wrist flexor muscles align with back-traced anatomical LMN counts.
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    Longitudinal assessment of mutant rats demonstrates progressive motor unit decline, more significantly in the hindlimb, which correlates strongly with plantarflexion muscle contractility.

Research Summary

The study refines CMAP and MUNE methods for assessing spinal motor unit input in rat forelimbs and hindlimbs, demonstrating robustness and alignment with anatomical LMN counts. Validation in SOD1 mutant rats showed progressive motor unit decline, particularly in the hindlimb, correlating with reduced muscle contractility. The research aims to improve cross-species translation using objective electrophysiological biomarkers to guide and improve bi-directional translation.

Practical Implications

Improved Biomarker Translation

Objective electrophysiological CMAP and MUNE values can be used as biomarkers to improve cross-species translation.

Neuromuscular Disease Modeling

The developed forelimb and hindlimb CMAP and MUNE techniques allow for spatial characterization of motor unit pathology in preclinical models of neuromuscular disease.

Assessment of Spinal Cord Injuries

The combined use of forelimb and hindlimb recording techniques can provide insights into topographic aspects of disease onset and progression in regard to regional loss of motor unit integrity, benefiting spinal cord injury research.

Study Limitations

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