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Impaired dynein function preserves spinal interneuron survival and positioning in an ALS-like mouse model
Eleni Christoforidou1, Jordan S Rowe1, Fabio A Simoes1
1Department of Neuroscience, School of Life Sciences, University of Sussex, Brighton, United Kingdom.
Plos One
|April 2, 2026
Summary
Impaired dynein function in cholinergic neurons does not cause interneuron loss or migration issues in the spinal cord, despite ALS-like symptoms. This suggests dynein's role in ALS involves axonal transport and neuronal physiology, not structural changes.
Area of Science:
- Neuroscience
- Cell Biology
- Genetics
Background:
- Cytoplasmic dynein is crucial for neuronal function.
- Impaired dynein function is linked to amyotrophic lateral sclerosis (ALS).
- The role of spinal interneurons in ALS pathogenesis is not fully understood.
Purpose of the Study:
- To investigate if reduced dynein function in cholinergic neurons affects the development, survival, or positioning of spinal inhibitory interneurons.
- To determine the contribution of interneuron deficits to ALS phenotypes.
Main Methods:
- Generated four mouse genotypes with graded reductions in dynein activity in cholinergic (ChAT+) cells.
- Analyzed lumbar spinal cords (L3-L6) at 52 weeks using immunostaining for ChAT, GAD-67, Parvalbumin, and Calbindin.
- Quantified cell numbers and radial positioning relative to the central canal, analyzing angular distributions.
Main Results:
- No significant genotype-dependent differences were observed in the numbers of interneurons (GAD-67+, Parvalbumin+, Calbindin+) or cholinergic neurons.
- Radial positioning of interneurons and cholinergic neurons remained preserved across genotypes.
- Minor angular shifts (5-10°) in cell distribution were observed but deemed unlikely to affect circuit connectivity.
Conclusions:
- Impaired dynein function in cholinergic neurons does not lead to interneuron loss or gross migratory defects in the lumbar spinal cord.
- ALS-like phenotypes in these models are more likely due to functional disruptions in axonal transport, synaptic maintenance, and neuronal physiology.
- The study clarifies that structural interneuron alterations are not the primary driver of ALS phenotypes in this context.
