Changes Of Pyramidal Neurons In Hippocampal CA3 And Nitric Oxide Level In Hippocampus In Rat Induced By Chronic Stress And Effects Of Phenytoin On Them

Background and Objective: Chronic stress is a precipitative cause of many physical and mental disorders. Hippocampus plays a vital role not only in learning and memory,and other psychological activities, but also in regulating negative feedback of hypothalamic-pituitary-adrenal (HPA) axis. Hippocampus has a plasticity, and is liable to damage during chronic exposure to many injurious factors. It is helpful to investigate the changes of neuroanatomy and neurochemistry of hippocampus induced by chronic stress for revealing the pathogenesis of stress-related mental disorders such as recurrent depression and posttraumatic stress disorder (PTSD). It was reported that Phenytoin (DPH), an anti-epileptic drug, blocked stress-induced atrophy of CA3 pyramidal neurons. The result suggests glutamate (Glu) plays a role in stress-induced atrophy of CA3 pyramidal neurons, as DPH is well- known to suppress Glu release. The purposes of this study are to research the effects of chronic stress on structure of hippocampal CA3 pyramidal neurons and level of nitric oxide (NO) in hippocampus in rat, meanwhile, to explore the effects of DPH on them. Material and Methods: Rats were divided into control group, stress group and stress-DPH group. Rats in stress group and stress-DPH were subjected to forced-swimming for four weeks, a 15-minute session a day. 4 DPH was injected intraperitoneally in stress-DPH group every before forced- swimming. Distilled water was injected intraperitoneally in the other groups in order to avoid the difference induced by injection. Using Nissl dye,Golgi staining and electron-microscope, we counted the number~ and observed structure of rat hippocampal CA3 pyramidal neurons in the three groups; Using the immunohistochemistty and the computerized image technique, we measured quantitatively the expression levels of rNOS and iNOS of rat hippocampal CA3 pyramidal neurons in the three groups. Nitric acid deoxidize en~rne method was used to examine NO levels of serum and hippocampal homogenate. Results: The number of hippocampal CA3 pyramidal neuron was significantly less in stress group (35.14?.85) than that in control group (38.74 ?3.54) and in stress-DPH group (38.41 ?2.23) (P<0.05); The total length of apical dendrite was significantly shorter in stress group (155.67 i-~ m?3.32 ~?m)than that in control group (195.63 ~t m?4.61 1-tm) and in stress-DPH group (198.10 i-~ m ?36.39 ~t m) (P<0.05). There were no significant differences in the number of cell and the total length of apical dendrite between control group and stress-.DPH group; The ultrastructural changes, including the solid-shrink of the whole cell, the reduction of the cell volume, the dissolution of plasmaleinma, the wrinkle of the nucleus membrane and the degeneration of the mitochodrions, were observed in hippocampal CA3 pyramidal neurons in stress group, and not in stress-DPH group and control group. The nNOS average grey degree in hippocampal CA3 pyramidal neurons was significantly lower in stress group (155.42?.77) than that in control group (164.54?.62) and in stress-DPH group (164.27?.55) (P<0.O1). As the average grey degree is correlated reversely with expression intensity, the decrease of nNOS average grey degree in stress group meant the increase of 5 nNOS expression during stress; The iNOS rel...