Activation of Glucagon-like Peptide-1 Receptor in Microglia Attenuates Neuroinflammation-induced Glial Scarring via Rescuing ARF and RHO GAP Adapter Protein 3 Expressions after Nerve Injury
The neuroinflammation is necessary for glial group initiation and clearance of damaged cell debris after nerve injury. The glucagon-like peptide-1 receptor (GLP-1R) agonist has been previously shown to have a neuroprotective effect in neurodegeneration, whereas its potency in microglial inflammation after SCI is still unknown.GLP-1R activation attenuated microglia-induced neuroinflammation by reversing M1 subtypes to M2 subtypes in vitro and in vivo. In addition, activation of GLP-1R in microglia blocked production of reactive astrocytes. We also found less neuroinflammation, reactive astrocytes, corrected myelin integrity, ameliorated histology, and improved locomotor function in SCI mice treated with Ex-4. Mechanistically, we found that Ex-4 rescued the RNA expression of Arf and Rho GAP adapter protein 3 (ARAP3). Knockdown of ARAP3 in microglia reversed activation of RhoA and the pharmacological effect of Ex-4 on anti-inflammation in vitro.
Keywords - Spinal Cord Injury, Exendin-4, Glucagon-like Peptide-1 Receptor, Inflammation, Arf and Rho GAP Adapter Protein 3