In vivo conversion of astrocytes to neurons in the injured adult spinal cord

Nat Commun., 2014 · DOI: 10.1038/ncomms4338 · Published: January 1, 2014

Simple Explanation

Spinal cord injuries (SCI) result in the irreversible loss of nerve cells and the formation of glial scars, leading to long-lasting neurological issues. A promising approach is to regenerate cells to replace those lost and repair the damage. This study demonstrates that astrocytes, a type of non-neuronal cell abundant in the spinal cord, can be directly converted into functional neurons by introducing a single transcription factor called SOX2. The conversion of astrocytes into neurons was further enhanced by valproic acid (VPA), a drug that modifies histone deacetylase. This suggests a potential regenerative strategy for SCI by reprogramming existing cells in the spinal cord.

Study Duration

Not specified

Participants

Adult male and female mice at 2–3 months of age

Evidence Level

Not specified

Key Findings

1
Ectopic SOX2 expression is sufficient to convert endogenous spinal astrocytes to proliferative DCX-positive neuroblasts in the injured adult spinal cord.
2
These induced neuroblasts can mature into synapse-forming GABAergic interneurons in vivo, which can further be promoted by VPA treatment.
3
The SOX2-mediated in vivo reprogramming is a slow process with neuroblasts and mature neurons not readily detectable until 4 wpi and 8 wpi, respectively.

Research Summary

This study demonstrates that resident astrocytes in the injured adult spinal cord can be manipulated to produce neurons by defined factors, raising the possibility of using these cells as a source for in situ repair of SCI. The SOX2-induced neurogenesis passes through a proliferation phase and can give rise to synapse-forming interneurons. The results of this study raise a promising potential for treating SCI through cellular regeneration by in situ conversion of patients’ endogenous glial cells to neurons.

Practical Implications

Potential Therapeutic Strategy

In situ reprogramming of endogenous astrocytes to neurons might be a potential strategy for cellular regeneration after SCI.

Reduced Obstacles to Clinical Application

This strategy might face fewer obstacles to clinical applications than other approaches since exogenous cells and transplantation are not required.

Synapse Formation

SOX2-induced adult neurogenesis can generate mature neurons with features of GABAergic interneurons in injured VPA-treated spinal cords that are capable of forming synapses with pre-existing ChAT+ motor neurons, suggesting potential integration into the local neural network of the injured spinal cord.

Study Limitations

1
The current reprogramming efficiency and the number of converted neurons are low.
2
Further studies are necessary to enhance the reprogramming process.
3
Further studies are necessary to define a precise strategy to generate subtype-specific neurons that are required for functional recovery after SCI.

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