Study On The Effect Of Zinc In Modulating Hippocamal Injuries Induced By Psychological Stress And Its Mechanisms

To explore the mechanisms underlying the insults of hippocampus induced by chronic psychological stress and the regulation role of zinc. Wistar rats were used to establish zinc deficiency and photo-electric stress models in order to observe the reactions of rats in different zinc status to chronic stress. Cell stress model was established to study hippocampal neuron injuries induced by CORT. The changes of Glu-NMDA receptor pathway and Ca2+-CaM system were detected in searching for the mechanisms underlying stress responses and stress-induced injuries. Rats treated by photoelectric stress showed abnormal behaviors in the open-field test while zinc deficiency made it worse, indicating that zinc status did affect the stress response ; The results of DNA ladder and TUNEL test showed that hippocampus was not only susceptive to zinc deficiency, but also sensitive to photo-electric stress. The results of in vitro study suggested a bilateral roles of zinc in regulating the cell damages caused by CORT: ameliorated by lower doses while aggravated by higher dose . The changes of [Ca2+]i-CaM system of hippocampal cells were observed in stressed rats; Glutamate uptake of hippocampus was also affected by stress which lead to prolonged high level of Glu in synaptic cleft. Both of these changes were more apparent in zinc deficiency rats than in other groups; CORT treated hippocampal cells showed decreased membrane resting potential(RP), by which the Glu uptake was inhibited; simultaneous addition of lower doses of zinc lead to no changes in RP; besides, the results of NMD A receptor binding test and NMDA receptor subtypes mRNA expression suggested that changes in the levels of NMDA receptor subtypes may be involved in stress/CORT induced neuron injuries. Zinc may exert regulating role on stress responses and its injuries from targeting on multisites mentioned above.