Removal of the Potassium Chloride Co-Transporter from the Somatodendritic Membrane of Axotomized Motoneurons Is Independent of BDNF/TrkB Signaling But Is Controlled by Neuromuscular Innervation

eNeuro, 2019 · DOI: https://doi.org/10.1523/ENEURO.0172-19.2019 · Published: September 20, 2019

Simple Explanation

Following peripheral nerve injuries (PNIs), a protein called KCC2 is lost from the surface of spinal cord motoneurons. This loss potentially affects how these neurons respond to inhibitory signals. The study investigated whether this KCC2 loss is influenced by microglia or a signaling pathway involving BDNF and TrkB, which are known to play roles in nerve injury responses. The research showed that KCC2 regulation in injured motoneurons is linked to neuromuscular innervation. KCC2 levels are restored when motoneurons reconnect with muscle.

Study Duration

3, 7, 14, 21, 28, or 60 days

Participants

Several lines of transgenic animals in addition to wild types (WTs) of both sexes were used.

Evidence Level

Not specified

Key Findings

1
KCC2 protein is lost from the somatodendritic membrane of axotomized spinal cord motoneurons after downregulation of kcc2 mRNA expression.
2
KCC2 dysregulation in axotomized motoneurons is independent of microglia, BDNF, and TrkB.
3
Downregulation of KCC2 occurs specifically while injured motoneurons are regenerating and might be controlled by target-derived signals.

Research Summary

This study investigated KCC2 regulation on spinal motoneurons after peripheral nerve injury, finding KCC2 loss occurs at the transcriptional level. KCC2 loss on axotomized motoneurons relates to muscle innervation, suggesting a dependence on target-derived signals. KCC2 loss in axotomized motoneurons may be part of the response that facilitates regeneration of motor axons in the periphery.

Practical Implications

Targeted Therapies

Understanding KCC2 regulation could lead to targeted treatments for neuronal injuries.

Regeneration Strategies

The link between KCC2 and nerve regeneration could improve recovery strategies.

Motor Function

The influence of GABA/glycine synapses on motor neuron activity can help better understand motor function.

Study Limitations

1
The study focuses on one motor pool axotomized after sciatic nerve injuries.
2
The exact mechanisms controlling target-derived signals in KCC2 regulation remain unclear.
3
The impact of partial retention of KCC2 density in mid-distal dendrite regions is yet unknown.

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