PTPσ Knockdown in Lampreys Impairs Reticulospinal Axon Regeneration and Neuronal Survival After Spinal Cord Injury

Front. Cell. Neurosci., 2020 · DOI: 10.3389/fncel.2020.00061 · Published: March 19, 2020

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

This study investigates the role of PTPσ, a protein, in nerve regeneration after spinal cord injury in lampreys. Unlike mammals, lampreys can recover from spinal cord injuries. The researchers reduced the amount of PTPσ in lampreys after spinal cord injury and then observed the effects on nerve regeneration and survival. They examined axon regeneration, cell death, and behavioral recovery. Unexpectedly, reducing PTPσ impaired nerve regeneration and neuron survival. This suggests that PTPσ is not a negative regulator of nerve regeneration in lampreys, contrary to what is seen in mammals.

Study Duration

10 Weeks

Participants

Wild-caught larval sea lampreys, approximately 8–12 cm in length (3–5 years old)

Evidence Level

Original Research

Key Findings

1
Knocking down PTPσ expression significantly impaired reticulospinal axon regeneration in lampreys, primarily due to reduced long-term neuron survival.
2
Cell loss following PTPσ knockdown was not preceded by an increase in caspase or p53 activation, suggesting a non-apoptotic mechanism of cell death.
3
PTPσ knockdown attenuated the local immune response to spinal cord injury, potentially affecting neuron survival and regeneration.

Research Summary

This study investigated the role of PTPσ in axon regeneration after spinal cord injury (SCI) in lampreys, which can recover from complete spinal cord transection. Using antisense morpholino oligomers (MOs) to knock down PTPσ expression after transection (TX), the researchers assessed the effects on axon regeneration, caspase activation, intracellular signaling, and behavioral recovery. Unexpectedly, PTPσ knockdown impaired reticulospinal (RS) axon regeneration due to reduced long-term neuron survival, without enhanced caspase activation, suggesting that PTPσ is not a net negative regulator of axon regeneration in lampreys.

Practical Implications

Re-evaluation of PTPσ Role

The study challenges the assumption that PTPσ universally inhibits axon regeneration, suggesting its role is context-dependent.

Further mechanistic studies

The mechanism underlying cell death following TX and PTPσ knockdown remains unknown, warranting further investigation.

Non-autonomous effects

Suggests non-autonomous processes at the site of injury may have contributed to impaired supraspinal RS neuron survival.

Study Limitations

1
The exact mechanism by which PTPσ knockdown enhanced TX-induced cell death was not identified.
2
Off-target effects of morpholino oligomers (MOs) cannot be completely ruled out.
3
The effects of PTPσ knockdown on specific cell types within the immune system were not fully characterized.

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