The regulatory role of NAAG-mGluR3 signaling on cortical synaptic plasticity after hypoxic ischemia

Synapses can adapt to changes in the intracerebral microenvironment by regulation of presynaptic neurotransmitter release and postsynaptic neurotransmitter receptor expression following hypoxic ischemia (HI) injury. The peptide neurotransmitter N-acetylaspartylglutamate (NAAG) exerts a protective effect on neurons after HI and may be involved in maintaining the function of synaptic networks. In this study, we investigated the changes in the expression of NAAG, glutamic acid (Glu) and metabotropic glutamate receptors (mGluRs), as well as the dynamic regulation of neurotransmitters in the brain after HI, and assessed their effects on synaptic plasticity of the cerebral cortex. Thirty-six Yorkshire newborn pigs (3-day-old, males, 1.0-1.5 kg) were selected and randomly divided into normal saline (NS) group (n = 18) and glutamate carboxypeptidase II inhibition group (n = 18), both groups were divided into control group, 0-6 h, 6-12 h, 12-24 h, 24-48 h and 48-72 h groups (all n = 3) according to different post-HI time. The content of Glu and NAAG after HI injury were detected by 1H-MRS scanning, immunofluorescence staining of mGluRs, synaptophysin (syph) along with postsynaptic density protein-95 (PSD95) and transmission electron microscopy were performed. ANOVA, Tukey and LSD test were used to compare the differences in metabolite and protein expression levels among subgroups. Correlation analysis was performed using Pearson analysis with a significance level of α = 0.05. We observed that the NAAG and mGluR3 expression levels in the brain increased and then decreased after HI and was significantly higher in the 12-24 h (P