GABA receptors regulate the neural stem cell potential of Pkd2l1 cerebrospinal fluid-contacting neurons via the PI3K/Akt signaling pathway.

Cerebrospinal fluid-contacting neurons (CSF-cNs) exhibit neural stem cell (NSC) properties both in vitro and in vivo, and they may play a critical role in recovery after spinal cord injury (SCI). GABA receptors (GABABRs) are expressed in Pkd2l1 CSF-cNs. However, their role in Pkd2l1 CSF-cNs still needs to be discovered. In this study, we observed a significant reduction in GABAR expression in a murine model 7 d after SCI. We further discovered that GABAR activation enhanced the proliferation of Pkd2l1 CSF-cNs while inhibiting apoptosis. Additionally, this activation mitigated vacuole loss and neuronal damage in the pericentral canal region of the spinal cord, attenuated myelin and axonal loss within the spinal cord, and facilitated motor function recovery in SCI model mice. Mechanistically, GABAR primed quiescent Pkd2l1 CSF-cNs for cell cycle reentry through the activation of PI3K/Akt signaling. Our findings suggest that GABAR activation enhances the NSC potential of Pkd2l1 CSF-cNs, ultimately enabling post-SCI recovery in murine models.