| First Author | Jiang C | Year | 2020 |
| Journal | iScience | Volume | 23 |
| Issue | 10 | Pages | 101570 |
| PubMed ID | 33083737 | Mgi Jnum | J:359414 |
| Mgi Id | MGI:6717830 | Doi | 10.1016/j.isci.2020.101570 |
| Citation | Jiang C, et al. (2020) PD-1 Regulates GABAergic Neurotransmission and GABA-Mediated Analgesia and Anesthesia. iScience 23(10):101570 |
| abstractText | The immune checkpoint inhibitor programmed cell death protein 1 (PD-1) plays a critical role in immune regulation. Recent studies have demonstrated functional PD-1 expression in peripheral sensory neurons, which contributes to neuronal excitability, pain, and opioid analgesia. Here we report neuronal expression and function of PD-1 in the central nervous system (CNS), including the spinal cord, thalamus, and cerebral cortex. Notably, GABA-induced currents in spinal dorsal horn neurons, thalamic neurons, and cortical neurons are suppressed by the PD-1-neutralizing immunotherapeutic Nivolumab in spinal cord slices, brain slices, and dissociated cortical neurons. Reductions in GABA-mediated currents in CNS neurons were also observed in Pd1 (-/-) mice without changes in GABA receptor expression. Mechanistically, Nivolumab binds spinal cord neurons and elicits ERK phosphorylation to suppress GABA currents. Finally, both GABA-mediated analgesia and anesthesia are impaired by Pd1 deficiency. Our findings reveal PD-1 as a CNS-neuronal inhibitor that regulates GABAergic signaling and GABA-mediated behaviors. |
