KCC2 downregulation after sciatic nerve injury enhances motor function recovery.

ABSTRACT: Injury to mature neurons induces downregulated KCC2 expression and activity, resulting in elevated intracellular [Cl^-] and depolarized GABAergic signaling. This phenotype mirrors immature neurons wherein GABA-evoked depolarizations facilitate neuronal circuit maturation. Thus, injury-induced KCC2 downregulation is broadly speculated to similarly facilitate neuronal circuit repair. We test this hypothesis in spinal cord motoneurons injured by sciatic nerve crush, using transgenic (CaMKII-KCC2) mice wherein conditional CaMKIIα promoter-KCC2 expression coupling selectively prevents injury-induced KCC2 downregulation. We demonstrate, via an accelerating rotarod assay, impaired motor function recovery in CaMKII-KCC2 mice relative to wild-type mice. Across both cohorts, we observe sim

SUBMITTER: Cheung DL 

PROVIDER: S-EPMC10185507 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature