Degeneration and impaired regeneration of gray matter oligodendrocytes in amyotrophic lateral sclerosis

Nat Neurosci, 2013 · DOI: 10.1038/nn.3357 · Published: May 1, 2013

Simple Explanation

Oligodendrocytes are brain cells that support nerve fibers. This study found that in mice with ALS, these cells degenerate in the spinal cord before the disease even starts. Although the body tries to make new oligodendrocytes, these new cells don't mature properly, leading to a loss of myelin, which is a protective coating on nerve fibers. Similar problems with oligodendrocytes were seen in the brains and spinal cords of people with ALS. Removing a problem gene from these cells in mice slowed down the disease, suggesting these cells play a role in ALS.

Study Duration

Not specified

Participants

ALS mice, human ALS patients

Evidence Level

Not specified

Key Findings

1
Extensive degeneration of gray matter oligodendrocytes occurs in the spinal cord of ALS mice before disease onset.
2
Newly formed oligodendrocytes in ALS mice fail to mature, resulting in progressive demyelination.
3
Selective removal of mutant SOD1 from oligodendroglia substantially delayed disease onset and prolonged survival in ALS mice.

Research Summary

The study reveals extensive degeneration of gray matter oligodendrocytes in ALS mice before disease onset, with impaired maturation of newly formed oligodendrocytes leading to demyelination. Oligodendrocyte dysfunction is prevalent in human ALS, as evidenced by gray matter demyelination and reactive changes in NG2+ cells in motor cortex and spinal cord. Selective removal of mutant SOD1 from oligodendroglia significantly delayed disease onset and prolonged survival in ALS mice, indicating a crucial role for these cells in ALS pathogenesis.

Practical Implications

Therapeutic Target

Oligodendrocytes represent a potential therapeutic target for ALS, focusing on promoting their survival and function.

Understanding ALS Pathogenesis

The study highlights the importance of non-neuronal cells, particularly oligodendrocytes, in the pathogenesis of ALS.

Treatment Strategies

Therapeutic approaches developed for multiple sclerosis, focusing on oligodendrocyte survival and metabolic support, may be beneficial for ALS.

Study Limitations

1
The study primarily uses mouse models of ALS, which may not fully replicate the human disease.
2
Further research is needed to fully understand the mechanisms underlying oligodendrocyte degeneration in ALS.
3
The relative contributions of primary oligodendrocyte death and secondary oligodendrocyte death due to Wallerian degeneration in human ALS tissues remains to be determined.

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