P2X7 receptor activation awakes a dormant stem cell niche in the adult spinal cord

Frontiers in Cellular Neuroscience, 2023 · DOI: 10.3389/fncel.2023.1288676 · Published: December 18, 2023

Simple Explanation

The spinal cord contains a dormant stem cell niche that can be reactivated after injury to generate new cells and limit damage. This study investigates how ependymal cells, a type of cell within this niche, are reactivated after injury, focusing on the role of ATP, a "danger signal" released upon tissue damage, and its interaction with the P2X7 receptor. The researchers found that activating the P2X7 receptor in mice via intraspinal injection of BzATP, a selective agonist, mimicked the effects of spinal cord injury by triggering cell proliferation and shifting cells to a GFAP phenotype, similar to that induced by injury. This activation also induced the expression of connexin 26 (Cx26), which is needed for proliferation after injury. The study suggests that the P2X7 receptor plays a crucial role in awakening the ependymal stem cell niche after injury. It also indicates that purinergic signaling, the process of cell communication using ATP and related molecules, could be a valuable target for enhancing the contribution of endogenous progenitors to spinal cord repair.

Study Duration

Not specified

Participants

Adult (P90-150) C57BL/6J mice

Evidence Level

Original Research

Key Findings

1
Activation of P2X7 receptors by BzATP in vivo rescued ependymal cells from quiescence, triggering a proliferative response similar to that generated by injury.
2
P2X7r activation by BzATP induced a shift of ependymal cells to a glial fibrillary acidic protein (GFAP) phenotype similar to that induced by injury.
3
In vivo blockade of P2X7r with the potent antagonist AZ10606120 reduced significantly the injury-induced proliferation of ependymal cells.

Research Summary

This study explores the role of the P2X7 receptor (P2X7r) in reactivating the ependymal stem cell niche in the adult spinal cord following injury. The ependyma is a latent stem cell niche that is reactivated by injury, generating new cells that migrate to the lesion site to limit the damage. The researchers simulated P2X7r activation using BzATP, a selective agonist, and observed that it rescued ependymal cells from quiescence, induced a GFAP phenotype shift, and increased connexin 26 (Cx26) expression, mirroring effects seen after spinal cord injury (SCI). Conversely, blocking P2X7r with AZ10606120 significantly reduced injury-induced ependymal cell proliferation. These findings suggest that P2X7r plays a key role in awakening the ependymal stem cell niche after injury, making purinergic signaling a potential therapeutic target for spinal cord repair.

Practical Implications

Therapeutic Target

Purinergic signaling, particularly the P2X7 receptor, could be a therapeutic target for promoting endogenous repair mechanisms after spinal cord injury.

Stem Cell Activation

Understanding the role of P2X7r in awakening the ependymal stem cell niche could lead to strategies for enhancing the regenerative capacity of the spinal cord.

Targeted Drug Development

Development of drugs that selectively modulate P2X7r activity could improve functional outcomes following spinal cord injury by promoting beneficial responses from endogenous progenitors.

Study Limitations

1
The study did not fully elucidate the downstream signaling pathways through which P2X7r activation promotes ependymal cell proliferation and phenotypic changes.
2
The study did not explore the long-term effects of P2X7r activation on spinal cord repair and functional recovery.
3
The study did not investigate the potential side effects of P2X7r modulation on other cell types in the spinal cord.

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