In addition to GABA mediated mIPSCs glutamate mediated minia
In addition to GABA-mediated mIPSCs, glutamate-mediated miniature excitatory postsynaptic potentials (mEPSCs) regulate the excitability of the nervous system. GluRs can be divided into ionic and metabotropic GluRs. Ionotropic GluRs can be pharmacologically differentiated by specific binding of the agonists NMDA, kainic apomorphine (KA), and AMPA, and are closely related with epilepsy . According to present study, the expression levels of GluA1-4, GluN1, GluN2A and GluN2B in the rat hippocampi was decreased after treatment with liraglutide, and increased after treatment with ex9-39, which can undermine the effects of liraglutide. Additionally, immunoprecipitation confirmed that GLP-1R interacted with the GluA and GluN subtypes, which suggested that GLP-1R activation can down-regulate the expression levels of the GluA and GluN subtypes in PTZ-treated rats. Based on many studies, GLP-1 analogs or agonists can reverse the expression of GluR in animal models of AD and exert favorable anti-AD effects. Exendin-4 can the levels of GluR1 subunits and postsynaptic density protein-95 in AD . Furthermore, treatment with GLP-1 analogue can effectively protect against the amyloid β peptide-induced decrease in mEPSCs, which shows that GLP-1/GLP-1R is highly probabilistic and closely related to synaptic plasticity . The above evidence suggests that the GLP-1R up-regulation can reverse the changes in GluRs and GluR-mediated mEPSCs. We thus hypothesized that increased expression of GluRs decreased the frequency and amplitude of GluR-mediated mIPSCs, leading to increased neuronal excitability and thereby triggering epilepsy. In contrast, up-regulation of GLP-1R reversed the expression of GluRs in seizure-induced rats, resulting in the decrease in neuronal excitability and thereby alleviating seizures.
Conflicts of interest
Acknowledgements This research has been strongly supported by Chongqing Health Bureau (2013-1-05) Foundation Quanhong Shi. We sincerely thank the patients for the donation of brains.