| ObjectiveMore and more observations suggested that depression was not a completely functional mental disorder; at least, structural changes were contributed to a part of it. Recently, it has been demonstrated that chronic mild stress could lead to depression. Chronic stress induced series of physiological and biochemical changes in the organism, especially in the central nervous system (CNS) , and eventually lead to structural damages of brain.When the pathogenesis of depression was studied, besides the changes of neurotransmitters, neural injury should also be considered. And decreasing the neural injury and protecting the brain from being damaged should be a new and important target for the treatment of depression.Immediate Early Gene (IEG) including c -fos is a family of pro-to - oncogene. Their expression could be induced in response to a wide range of stimuli. The protein products regulated the transcription of their target genes as " third messengers". It has been proved that the expression of c - fos could be used as a marker to follow the functional activity of neurons.It is well known that the hippocampus is one of the most important brain regions that regulate the response to the stress. Moreover,the hippocampus is one of the regions most susceptible in response to the stress because it possesses of two types of receptors of corticoste-roids.In the present study, we used the expression of c - fos as the marker indicating the neural activity in the hippocampus of rats being exposed to repeated or chronic and comprehensive stress to study the relation between the expression of c - fos and the structural and functional changes in the hippocampus. This would help to study the path-ogenesis of depression, and would provide basis for the treatment of depression.Materials1 Experimental animals: Male Wistar rats (n=45) weighting a-bout 200 - 300g were purchased from the center of experimental animals in China Medical University.2 Experimental reagents: Rabbit anti - c - FOS and SABC kit ( Boster Biotechnology Co. LTD. )3 Experimental instruments: Electrophysiological apparatus, Meta Morph / Cool Snapfx /Ax70 image analysis system.MethodsExperimental rats were housed for 7 days to adapt the conditions of the lab. After that, they were divided into 3 groups ( n = 15/group) randomly on the basis of their weights and the results of Open - field test.The rats in group A were exposed to forced - swimming stress onthe 22nd day only. The rats in group R were exposed to repeated forced - swimming stress everyday for consecutive 7 days. Group C received various types of stresses everyday for consecutive 21 days followed by a forced swimming stress on the 22nd day.. Open - field tests were carried on each rat before the last stress.0, 30, 60, 120 and 240 min after the beginning of the last swimming stress, 3 rats were selected from each group to be anaesthetized with 60 mg /kg (i. p. ) of sodiumpentobarbital and perfused via left ventricle with 200ml saline followed by 300ml 4% paraformaldhyde. Brains were removed and postfixed for more than 48h. Then the brains were dehydrated through graded - concentration ethanol and embedded in olefin. And sections were cut coronally.Immunohistochemistry method was used to measure the expression of FOS protein in the hippocampus. 4 pieces of sections of every rat were analysed on image analysis system. One - way ANOVA was used to compare the differences in the expression of FOS between each group or between each time point of a group with spss 11.0 statistic software.Results1 Neurons under light microscope Compared with group A, the distance between CA3 pyramidal neurons increased and the amount of the neurons decresed in group C, but not in group R.2 Weight and the result of Open - field test After 6 - day stress, group A and R had no difference in weight. Open - field measures showed that stopping time in the center of group R increased compared with group A. Ambulation, rearing and grooming decreased and defe-... |
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