GABA promotes survival and axonal regeneration in identiﬁable descending neurons after spinal cord injury in larval lampreys

Cell Death & Disease, 2018 · DOI: 10.1038/s41419-018-0704-9 · Published: June 22, 2018

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

This study investigates the role of GABA, a neurotransmitter, in promoting the survival and regeneration of nerve cells after spinal cord injury (SCI) in lampreys. The researchers found that GABA, acting through specific receptors, can reduce cell death and encourage the regrowth of axons, which are essential for nerve function. By manipulating GABA signaling, the study demonstrates that endogenous GABA promotes axonal regeneration after a complete SCI in lampreys by activating GABAB receptors.

Study Duration

1-12 weeks post-lesion

Participants

115 larval sea lampreys

Evidence Level

Not specified

Key Findings

1
GABA and baclofen treatments significantly reduced caspase activation in descending neurons 2 weeks after a complete SCI.
2
Long-term treatments with GABOB and baclofen significantly promoted axonal regeneration of descending neurons after SCI.
3
Knockdown of GABAB receptors inhibited axonal regeneration, confirming the role of endogenous GABA in promoting regeneration after SCI.

Research Summary

This study demonstrates that GABAergic signaling through GABAB receptors promotes both the survival and axonal regeneration of descending neurons in larval sea lampreys following spinal cord injury (SCI). The researchers used in situ hybridization to confirm the expression of GABAB receptors in descending neurons and observed an acute increase in their expression after SCI, suggesting a neuroprotective role for GABA. Gain- and loss-of-function experiments further validated that GABA and its agonists reduce caspase activation (a marker of cell death) and promote axonal regeneration, while blocking GABAB receptors inhibits axonal regeneration.

Practical Implications

Therapeutic Target

GABAergic signaling could be a potential therapeutic target for promoting neuronal survival and axonal regeneration after SCI.

Clinical Translation

Existing drugs like baclofen, already used for spasticity in SCI patients, could be further explored for their regenerative potential.

Understanding Neurotransmitter Systems

The study highlights the importance of understanding changes in neurotransmitter systems after SCI for developing effective neuropharmacological interventions.

Study Limitations

1
Behavioural analyses were not performed to establish a relationship between increased regeneration and improved functional recovery after the treatments.
2
The morpholino experiments suggest that GABA might promote regeneration by activating GABAB receptors expressed in the axotomized descending neurons.
3
The study was conducted in lampreys, and further research is needed to translate these findings to mammalian models of SCI.

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