| Objective: With the increase of the competitive pressures frommodern society, more and more people have been suffering from depression.The previous researches proved that the clinic depression was associated withall kinds of mild chronic stresses from daily life, and the behaviours observedin chronic unpredictable mild stressed rats may imitate the symtoms fromdepressed patients. Therefore, the model of rat was established by the chronicunpredictable mild stressed methods in the study, the hippocampal microRNAsexpression profile were detected in the successful model of rat, and the differentmicroRNAs were screened to analyze its target genes. The study may providenew ways and means for the future clinical diagnosis and treatment ofdepression induced by stress. Method: Forty adolescent female SD rats selectedby baseline level were randomly divided into normal group and model group;the rats in normal group were fed normally with five per cage; the rats in modelgroup were fed with one per cage and were randomly daily stimulated by amild stressor from fourteen different kinds of mild stressors(e.g. nyctohemeralrhythm inversion; cage tilt; fasting or/and drink-deprivation; noise; soiledcage;presence of a foreign object in the home cage;empty cage; tail hung up;paired housing; level shake; change of cage mate), which were changedeveryday and lasted for35consecutive days. At the28th and35th day aftertreatment, weigh, physical score, sucrose preference percent and open-field testscore of rats of the two groups were evaluated; The definition of successfulmodel rats：compared with the normal control group, the two times abovemonitoring indexes of the rats from the model group have obvious statisticaldifferences. The cerebral sucrose metabolism images of rats from successfulmodel and normal group were observed by18F-FDG PET/CT. Then, the rats were executed under anesthesia, and the hippocampus tissues were collected forHE staining and microRNAs array chip analysis. According to the results fromthe above microRNA assay chip, the target gene of these microRNAs werepredicted by bioinformatic analysis，and the functions and signal pathways ofthese target genes were investigated by GO and KEGG analysis.Results:12successful model rats were obtained from the model group, the weight, sugarpreference percentage and open-field score of the12rats were obviously lowerthan normal rat（sP<0.05）, the physical score were also significantly higher thannormal rats（P<0.05）; The cerebral18F-FDG PET/CT showed that the glucosemetabolism rate of successful model rats were significantly lower than normalrats in the regions of CIC, RSA, S2, Au1,SIBF, VPM(P<0.05). HE stainingshowed that hippocampal pyramidal cells of successful model rats becamethinner, were arranged in disorder and were irregular in shape with manypyknotic cells. The microarray chip analysis found that7microRNAs weresignificantly upregulated（miR-543-5p, miR-382-3p, miR-183-5p, miR-3573-5p,miR-410-5p, miR-202-3p, miR-493-3p）（P<0.05）, and1miR-370-3p wassignificantly downregulated（P<0.05）. miRNA target gene prediction andfunctional annotation analysis showed that there were significant enrichment inseveral GO Terms and pathways associated with depression (e.g. Amino acidimport;Interleukin-8biosyntheeic process; Cell adhesion molecules;Cholinergic synapse; Glutamatergic synapse; Caffeine metabolism; Glycerop-hospholipid metabolism;Neurotrophin signaling pathway; Notch signalingpathway;Toll-like receptor signaling pathway). Conclusion:Abnormalexpression of hippocampal multiple microRNAs were detected in chronicunpredictable mild stress rats, and these microRNAs may be related todepression-like behavior induced by stress. |
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