Protective effect of GLP-1 receptor agonists on synaptic plasticity in neonatal hypoxic-ischemic brain injury model mice

Abstract:

Objective To investigate the protective effect of glucagon-like peptide-1 receptor（GLP-1R） agonist（NLY01） on synaptic plasticity in neonatal hypoxia ischemia（HI） model mice.Methods In experiment 1，P7 mice were assigned to one of the following four groups，n=16/group：control group （Con group）， HI group， NLY01 group and HI+NLY01 group. In experiment 2， P7 mice were assigned to four groups（n=8/group）：HI group， HI+NLY01 group， HI+Ex9-39 group and HI+NLY01+Ex9-39 group. Among them， Ex9-39 was used to block GLP-1R. Behavioral tests were performed to measure learning ability. Golgi staining was used to measure dentate gyrus synaptic plasticity. Expression of synaptic and neuroinflammation-related proteins was assessed by Western blotting and immunofluorescence.Results Activation of GLP-1R by NLY01 prevented the emotional and cognitive deficits caused by HI. NLY01 prevented HI-induced reduction in GLP-1R levels. Activation of GLP-1R significantly ameliorated the impairment of synaptic plasticity，prevented the upregulation of inflammatory factors，and suppressed nuclear factor-κB（NF-κB） phosphorylation and microglial M1 polarization. In the HI model，the protective effect of NLY01 on HI-induced neonatal mice was blocked by Ex9-39.Conclusion GLP-1R may be a functional target regulating inflammatory pathways in acute brain injury in neonatal mice，supporting a potential therapeutic role of GLP-1R agonists in HI-induced neonatal mice.