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Updated: Jun 21, 2026
In Vivo Electrophysiological Measurement of Compound Muscle Action Potential from the Forelimbs in Mouse Models of Motor Neuron Degeneration
Published on: June 15, 2018
The primary locus of motor neuron death in an ALS-PDC mouse model
Grace Lee1, Tony Chu, Christopher A Shaw
1Department of Experimental Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Abstract:
A mouse model of amyotrophic lateral sclerosis-parkinsonism-dementia complex based on the consumption of cycad seed flour was used to determine whether the observed pathology of motor neuron loss begins in the distal axons or the spinal cord. Assessments of neuromuscular junction integrity and motor neurons were performed at multiple time points. Mice fed cycad pellets performed worse on the wire hang than controls. Microglial activation in cycad-fed mice was observed with motor neuron degeneration at 12 weeks, but reactive astrocyte proliferation was not observed. After 33 weeks of cycad feeding, motor neuron loss had stabilized, with no evidence of neuromuscular junction endplate denervation. These data suggest that neuronal pathology begins at the soma and proceeds distally in a 'dying forward' pattern.
Insights
This study investigated neurodegeneration in a mouse model of amyotrophic lateral sclerosis-parkinsonism-dementia complex. Findings suggest motor neuron pathology originates in the cell body and progresses distally, impacting motor function.
Area of Science:
- Neuroscience
- Neurodegenerative diseases
- Toxicology
Background:
- Amyotrophic lateral sclerosis-parkinsonism-dementia complex (ALS-PDC) is a devastating neurodegenerative disease.
- Cycad seed flour consumption is linked to ALS-PDC, but the precise mechanism of neurodegeneration remains unclear.
- Understanding the origin of motor neuron loss is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the spatiotemporal progression of motor neuron pathology in a mouse model of ALS-PDC induced by cycad seed flour.
- To determine if neurodegeneration begins in the distal axons or the spinal cord.
Main Methods:
- A mouse model was established using cycad seed flour consumption.
- Neuromuscular junction integrity and motor neuron assessments were conducted at multiple time points.
- Behavioral tests (wire hang) and histological analyses (microglial activation, astrocyte proliferation) were performed.
Main Results:
- Cycad-fed mice exhibited impaired motor performance compared to controls.
- Microglial activation and motor neuron degeneration were observed at 12 weeks.
- Motor neuron loss stabilized by 33 weeks with no evidence of neuromuscular junction denervation.
- Reactive astrocyte proliferation was not observed.
Conclusions:
- The data indicate that neuronal pathology in this ALS-PDC model initiates at the soma (cell body).
- Neurodegeneration follows a 'dying forward' pattern, progressing from the cell body to distal axons.
- These findings provide critical insights into the pathogenesis of ALS-PDC.
