SMA-related gene activity affects nerve cells differently in worm study
Different types of nerve cells respond differently when activity of a gene linked to spinal muscular atrophy (SMA) is reduced — and responses can vary even among nerve cells of the same type, according to a new study using nematode worms.
These findings shed new light on the underlying biology of SMA, researchers said in the study, “Individual C. elegans neurons display differential sensitivity to smn-1 silencing,” which was published in Life Science Alliance.
Reduced gene activity reveals differences in nerve cell vulnerability
SMA is mainly caused by mutations in the gene SMN1. Without a functional version of this gene, motor neurons — the nerve cells that control movement — gradually become damaged and die. Although it is well established that SMN1 mutations cause motor neuron problems in SMA, the molecular details of why these cells are especially vulnerable remain incompletely understood. It is also unclear how the mutations affect other types of nerve cells.
Caenorhabditis elegans is a type of nematode worm commonly used as a model organism in scientific studies. Its anatomy is much less complex than that of a human, which can offer distinct advantages for researchers. In particular, the worm’s nervous system has been fully mapped, allowing scientists to identify distinct classes of neurons, or nerve cells, with relative ease.
In this study, scientists engineered nematode worms in which activity of the worm counterpart of SMN1 was selectively reduced in one type of nerve cell. In some worms, it was reduced only in a specific group of motor neurons. In others, it was reduced only in touch receptor neurons (TRNs), which let the worms sense when they are being touched. The researchers noted that sensory neurons also may be affected in more severe cases of SMA.
“In this study, we took advantage of the simple and fully mapped nervous system of C. elegans to track SMA-associated neuronal alterations,” the researchers wrote.
Motor and sensory nerve cells show different vulnerability patterns
“Together, these findings indicate distinct vulnerability profiles among [motor neuron] subtypes and between individual cells with those subtypes,” the researchers wrote.
TRNs with reduced SMN1 activity also showed some defects, but the specific changes differed from those seen in motor neurons and varied among TRN subtypes. Specifically, TRNs that form during the first larval stage were often not detectable when expected, suggesting delayed development and possibly greater susceptibility to degeneration.
Collectively, the findings suggest that “neuronal susceptibility is not strictly determined by cell class identity but may instead depend on intrinsic neuronal properties, functional state, and developmental context,” the researchers concluded.
“Our observation of distinct responses to [reduced activity of the SMA-related gene] in individual C. elegans neurons provides a foundation for investigating the molecular mechanisms involved in differential sensitivity, ultimately contributing to a better understanding of neurodegenerative disease,” they added.
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