Chronic Stress Depression Sample Behavior High Cysteine In Hippocampus Glutamic Acid And Its Receptor Regulation

Depression is an emotional and mental disorder which characterized by emotional persistent low, with many psychiatric symptoms such as long-lasting low emotion, thinking slowly and speech acts reduction. Depression not only damages the individual’s physical and mental health, but also causes a socio-economic loss. Depression occurs universally, however, due to the complexity of its pathogenesis, its causes and mechanism is not yet clear and still debatable. However, a large number of studies have shown that the stress is one of the main factors induced depression. The hippocampus is the main structure of the limbic system and it plays an important role in the regulation of emotional behavior and neuroendocrine function. Due to the close relationship between hippocampus and dopamine system in the prefrontal cortex and the midbrain, hippocampus will always be one of the high-profile brain areas interrelated with the emotional behavior. Extensive literature have shown that the stress leads to an increase in hippocampal Glu level, and the over-activation of NMDA receptors may be the main cause of stress induced depression, NMDA receptor antagonists have a significant antidepressant effect, chronic treatment of antidepressants can also increase the expression of AMPA receptor in rat hippocampus. However, it is still unclear that the specific mechanism of the stress-induced hippocampal Glu levels increase and over-activation of NMDA receptors, and whether hippocampal astrocytes and glutamatergic neurons have interaction with the Glu and its receptors disorder.Homocysteine (Hcy) is a kind of key intermediate in the metabolism of methionine and cysteine. A large number of studies have shown that high hyperhomocysteinemia have a connection with the genesis and development of depression, cognitive impairment, Alzheimer’s disease, Pa Parkinson disease and other neurological or psychiatric diseases. Studies suggest an association of depression with high homocysteine in blood plasma,52%of depression patients have higher levels of Hcy than others. The change of Hcy levels in brain has not been reported. Research has shown that only astrocytes produce and release Hcy in central nerve system, and over-dose of glutamate (Glu) can stimulate astrocytes to release Hey, which damages the hippocampus neurons. Hey acts by Glu and N-methyl-D-aspartic acid (NMDA) receptor. However, it is still unclear that whether Hey participates the genesis of stress-induced depression-like behavior and whether the change of animals’emotion and behavior relates to the Glu, NMDA receptor and AMPA receptor in the hippocampus.Our study was to investigate the role of Hey which was released by hippocampal glial cells and its relationship with NMDA receptor and AMPA receptor in depression induced by chronic unpredictable mild stress (CUMS) and explore the mechanism of changes in Glu/Glu receptors in glial cells and neurons. CUMS depression model was established. The weight of rats was weighed on the1st,7th,14th, and21st days during the experiment. The behavioral performances were observed by means of sucrose consumption test, open field test and tail suspension test. Intrahippocampal microinjection of Hey, NMDA receptor antagonist MK-801and AMPA receptor antagonist NBQX was performed under stereotaxic guide cannula. The concentration of Glu and the expression of its receptors’subunits were detected respectively by High performance liquid chromatography (HPLC) and Western blot. The Hey content and the level of phosphorylation of NMDA receptor and AMPA receptor in hippocampus were separately detected by enzyme linked immunosorbent assay (ELISA).Our data suggest that CUMS significantly induced the depressive-like behaviors in rats,and the content of Glu and Hey, the expression of NMDA receptors’subunits NR1/NR2B and the level of phosphorylation of NMDA (p-NMDA) in hippocampus had increased significantly, while the expression of AMPA receptors’subunits GluR2/3and the level of phosphorylation of AMPA (p-AMPA) receptors had decreased significantly. Microinjection of Hey into hippocampus resulted in the similar depressive-like behaviors and an increased Glu content compared to the CON/SAL group, the expression of NR1/NR2B/GluR2/3and the level of p-NMDA had increased significantly, but the level of p-AMPA receptors had reduced observably. Intrahippocampal injections of MK-801had effectively improved the depression-like behaviors induced by CUMS and Hey, and the elevation of Glu content induced by Hey in hippocampus was attenuated in MK-801injection, whereas NBQX can not improve the depression-like behaviors, the Glu content induced by Hey was declined remarkably. These results suggest that CUMS may contribute to the production and release of Hcy via hippocampal astrocytes. As the expression of NR1/NR2B/GluR2/3and the level of p-NMDA increased, Hey results in the elevation of Glu level and the decrease of p-AMPA receptors level, which leads to depressive-like behaviors in the end. In a word, Stress leads to depression-like behavior that may be induced by the increased release of Hcy from astrocytes which results in the elevation of hippocampal Glu and the alteration of expression and phosphorylation level of NMDA receptor and AMPA receptor.