| Major depression disorder(MDD)is a mental illness that is affected by both genes and the environments.The number of MDD patients in the world has exceeded 300 million,which is extremely harmful to individual health and social development.The drug development work for MDD has been carried out as early as the 1950 s.The research and development of drugs mainly focused on the hypothesis of 5-hydroxytryptamine(5-HT).Most drugs have a slow onset,long cycles are required,and expensive with a lot of side effects.Metformin(Met)is the first-line drug for the treatment of type 2 diabetes mellitus(T2DM).Clinical studies have found that many T2 DM patients have a higher incidence of MDD,and the Met potential targets are associated with many MDD-related genes.However,if Met may have a therapeutic role on MDD is largely unclear.The low-dose Lipopolysaccharide(LPS)was used to continuously inject the mice to establish MDD mice model,then the behaviors of mice were detected by forced swimming test(FST)and tail suspension test(TST).It was found that the time of static immobility was significantly increased in LPS induced mice.Morphological examination showed that there was no change in the morphology and structure of the mouse brain.Electrophysiological recording showed that the frequency of the miniature excitatory postsynaptic currents(mEPSCs)increased in LPS induced mice,but the amplitude unchanged.We injected Met into MDD mice model,and the behavioral tests of FST and TST showed that the time of static immobility in MDD mice was reduced to normal level.Morphological examination showed that Met had no effect on the brain structure.Electrophysiological recording showed that increased frequency of mEPSCs and presynaptic glutamate release in LPS-induced MDD mice model were rescued to the normal level through Met injection.Our results suggest that the therapeutic effect of Met on MDD may be achieved by inhibiting the release of presynaptic excitatory neurotransmitters. |
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