| BackgroundDepression has become an important global public health problem. Studies have shown that the integrity of the white matter of the frontal lobe of the brain, the corpus callosum, hippocampus is obvious defect in patients with depression. There are a large numbers of nerve fiber bundles in cerebral white matter, which play a role in conducting nerve signal. Many studies have confirmed that injury in white matter is closely related with the occurrence of depression. Enriched environment can not only increase the total length and volume of myelinated fibers in the white matter, but also promote the proliferation of oligodendrocyte. The treatment with fluoxetine for short term can improve the integrity of white matter in patients with depression. This study explores the impact of enriched environment combined with fluoxetine on the behavior and white matter of rats induced with CUS by establishing the depression model of rats induced with chronic unpredictable stress (CUS), intervening with enriched environment and fluoxetine and taking frontal lobe, corpus callosum and hippocampus as the object brain regions.Objective1. To explore the impact of enriched environment combined with fluoxetine on the behaviors of rats induced with CUS.2. To explore the influence of enriched environment combined with fluoxetine on the maker of myelin (myelin basic protein, MBP) and oligodendrocytes (cyclic neucleotide phosphodiesterase, CNP).Methods1. The experimental animal grouping and the establishment of depression models.65 SPF male SD rats were assessed with open field tests to separate the unqualified.10 rats were randomly chosen as normal control group (A), which were raised in the standard environment. The models of depression were established with the left rats (raised in single house) in CUS method, among which 40 depression rats were randomly divided into depression model group (B), fluoxetine group (C), enriched environment group (D), fluoxetine combined with enriched environment group (E).2. The intervention with fluoxetine and enriched environment. Group C were given antidepressants fluoxetine at a dose of 10mg/kg.day with gavage. Group D were intervened with enriched environment for 12 hours/day. Group E were given fluoxetine at a dose of 10mg/kg.day and enriched environment for 12 hours/day at the same time.3. Behavioral assessment. All rats were assessed with the changes of body weight, sucrose consumption test and open field test respectively before the stimulation of CUS and the 21th day after the stimulation of CUS, on the first weekend, second weekend and third weekend during the interventions with fluoxetine intervention and rich environment to evaluate the behavioral changes.4. Experimental method. The contents of MBP, CNP in hippocamal subrigions, prefrontal lobe and corpus were detected with immunohistochemistry. The expression level of MBP mRNA, CNP mRNA in hippocamal subrigions, prefrontal lobe and corpus were detected with RT-PCR.5. Statistical method. The experimental data were analyzed with SPSS20.0 statistical software package. Multiple groups of measurement data were processed in one-way analysis of variance (one-way ANOVA). When there was homogeneity of variance, LSD method was applied, or Kruskal-Wallis Test was applied. Independent samples t test and paired t test were applied when comparing between two groups. P<0.05 was considered as statistically significant.Results1. The behavioral assessmentBefore the stimulation of CUS, there was no significant difference (P>0.05) in body weight, open-field test and sucrose consumption among the five groups. There was significant difference (P<0.05) in the changes of body weight, open-field test and sucrose consumption in group A, group C, group D and group E compared with those in group B after 21 days with the stimulation. On the first weekend of the intervention with fluoxetine and enriched environment, part of behaviors in group C, group D and group E had been improved when comparing with that in group B, especially in group E. On the second weekend of the intervention, the behavior in the groups E showed significant differences compared with that in group B, but there was no significant differences among group C, group D, group E and group A (P>0.05). On the third weekend of the intervention, it showed the same result with that on the second weekend.2. The content of MBP and CNP protein in hippocampus, prefrontal lobe and corpus callosumThere was no obvious difference of the content of MBP, CNP protein in corpus callosum area among the 5 groups. However, there were significant differences of MBP protein content in hippocampal CA1, DG and prefrontal lobe (F=6.956, P=0.000;F=6.098, P=0.001; F=6.590, P=0.000), in which the content in group B was lower than other 4 groups and revealed a significant difference (P<0.05). And there was no significant difference among group C, group D, group E and group A (P>0.05). Similarly, there were significant differences for CNP protein content in hippocampal CA1, DG and prefrontal (F=7.277, P=0.000; F=4.937, P=0.002; F=7.431, P=0.000), in which the content in group B was lower than other 4 groups to show a significant difference (P<0.05). And there was no significant difference among group C, group D, group E and group A (P>0.05).3. The expression level of MBP mRNA and CNP mRNA in hippocampus and prefrontal lobeThere were obvious differences of expression level of MBP mRNA in hippocampus and prefronta among 5 groups (F= 2.872, P= 0.044; F= 3.156, P= 0.031), in which the expression level in group B was much lower than that in other 4 groups (P<0.05). And there was no significant difference among group C, group D, group E and group A (P>0.05). Similarly, there were significant differences of CNP mRNA expression level in hippocampal CA1, DG and prefrontal lobe (F= 4.283, P= 0.009; F= 2.829, P=0.046), in which the expression level in group B was much lower than that in other 4 groups (P<0.05). And there were no significant difference among group C, group D, group E and group A (P>0.05).Conclusion1. The intervention of enriched environment and (or) fluoxetine can reverse the depression-like behavior in rats, the intervention of enriched environment combined with fluoxetine shows that it can promote the reversion of depression behavior.2. MBP, CNP protein contents and mRNA expression in hippocampal CA1, DG and prefrontal lobe obviously reduced in rats induced with CUS.3. The intervention of enriched environment and (or) fluoxetine can promote the contents of MBP and CNP and the expression level of mRNA in hippocampal CA1, DG and prefrontal lobe. |
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