Gamma-aminobutyric acid (GABA) promotes recovery from spinal cord injury in lampreys: role of GABA receptors and perspective on the translation to mammals

In lampreys, GABA is massively released after a complete SCI and it accumulates around some of the axotomized axons of reticulospinal neurons (Fernández-López et al., 2014). [...]we found a significant correlation between GABA accumulation and a high survival ability of the corresponding neurons (Fernández-López et al., 2014). Treatments with GABA [or GABOB (a GABA analogue)] and baclofen (a GABAB agonist) inhibited caspase activation and promoted axonal regeneration in identifiable reticulospinal neurons after a complete SCI in lampreys. [...]a morpholino treatment showed that endogenous GABA acts as a pro-regenerative factor by activating GABAB receptors expressed in descending neurons after a complete SCI in lampreys (Romaus-Sanjurjo et al., 2018). (2012) showed that the application of muscimol to the dorsal root ganglion of rats restored protein expression of peripheral myelin protein 22, which is a protein of the basal lamina that plays a key role in peripheral myelin formation and nerve regeneration. After CNS injuries, there is a downregulation of the KCC2 protein and no change in the expression of NKCC1 [Figure 1]B, which increases the [Cl–]i leading to depolarizing GABAA receptor-mediated responses, like during development (Payne et al., 2003) [Figure 1]B. It has been shown that the GABAA-induced [Ca2+]i increase is required for neurons to become dependent on brain-derived neurotrophic factor (BDNF) for survival (Shulga et al., 2008).