| Exercise has been shown to be able to improve depressive symptoms when used as an adjunct to medication. Nevertheless, the mechanisms underlying the antidepressant effect of exercise are not well understood. There have been previous studies showing that running exercise could induce brain angiogenesis and increasing the density of capillary in the brain. Also, the change of capillaries in the white matter has been discovered in the rats of depression. However, there have been no studies investigating the effects of running exercise on the volume density, length density, surface area density, total volume, total length and total surface area of the capillaries in the white matter of depression model of rat. The current study was designed to investigate the effects of running exercise on the capillaries in the white matter of depression model of rat using the new unbiased stereological methods. The present study found that there were significant differences in the effects of running exercise on the total volume of the white matter and the total length, total volume and total surface area of the capillaries in the white matter between running group rats and model control rats. Our results also revealed that exercise-induced increases of the capillaries in the white matter might be one of the structural bases for the treatment of the depression. These results provided important parameters for further studies of the mechanisms of vascular factors in depression and a new research direction for the development of a new clinical antidepressant means.Part one1 Materials and methods1.1 Male SD rats,180-220 g, provided by the Experimental Animal Center of Chongqing Medical University. After sugar consumption test and open-field test, they were randomly divided into model group and control group averagely. In the light of Willner and other references, we made some improvement to build the CUS rat model of depression. Model group was given five weeks of chronic unpredictable stimulus, while the control group was left undisturbed in the home cages except for the necessary controls such as regular cage cleaning and weighing. A sugar consumption experiment was performed to estimate depressive state in rats weekly. The open-field test would be only done in the fifth week.1.2 After the behavior tests, all brains were taken out. Five rats were randomly selected from the model group and control group as stereological study object respectively. Each hemisphere was cut into serial 1mm parallel slabs coronally. The slabs were photographed under anatomical microscope with a magnification of 10X. The white matter volume was calculated according to the Cavalieri’s principle.1.3 Five tissue blocks were randomly sampled from white matter in a systematic random fashion. Four sections with the thickness of 4 μm were cut from each sampled block. From each cut section,10-15 fields of view were randomly photographed under stereology microscope with a magnification of 6000.1.4 The length density and total length, volume density and total volume, surface area density and total surface area of the capillaries in the white matter between the two groups were calculated using stereological methods.2 Results2.1 The percentage of 24-hour sucrose consumption and total score of open-field test were decreased in model group significantly when compared with control group. (P<0.05).2.2 The total volume of the white matter in model group has a downward trend, but the difference was not significant when compared with control group. (P> 0.05).2.3 The length density and total length of capillaries in the white matter in model group were reduced significantly when compared with control group. (P<0.05).2.4 The volume density and total volume of capillaries in the white matter in model group have a reduction, and the difference was significant when compared with control group. (P<0.05).2.5 The surface area density and total surface area of capillaries in the white matter in model group have a downward trend, but the difference was not significant when compared with control group. (P> 0.05).Part two1 Materials and methods1.1 Male SD rats,180-220 g, were provided by the Experimental Animal Center of Chongqing Medical University. After sugar consumption test and open-field test, they were divided into model group (30) and control group (10). Using the former method,20 rats were selected randomly and divided into model control group and running groups averagely. In the running group, the animals run on a six-lane motorized treadmill for four consecutive months with 20 min each day and five consecutive days each week. The vacuity control, rats and model control rats were housed under identical conditions without running. In the eighth week, both sugar consumption test and open-field test were done.1.2 After completion of behavioral experiments, five rats in each group were randomly selected and used for the stereological analyses.2 Results2.1 In the fourth week, the percentage of sugar consumed in sucrose preference test in model group was significantly lower than the vacuity control group (P<0.01), and four weeks running exercise had a positive effect on the sucrose preference. Compared with the model control group, the percentage of sucrose preference of running group was significantly higher (P<0.05); the percentage of sucrose preference between the running group and the vacuity control group was not significantly different (P> 0.05).2.2 In the fourth week, the total score of model group was significantly lower than the vacuity control group (P<0.01), after four-week running exercise, the total score of running group had an increasing trend, but compared with both the model control group and the vacuity control group, there had no significant difference respectively (P> 0.05).2.3 The difference of white matter volume was significant between running group and model control group (P<0.05); the white matter volume between the running group and the vacuity control group was not significantly different (P>0.05).2.4 The differences of the length density and total length of capillaries in the white matter were significant between the running group and model control group (P<0.05); the length density of capillaries in the white matter between the running group and the vacuity control group was significantly different (P<0.05); the length of capillaries in the white matter between the running group and the vacuity control group was not significantly different (P>0.05).2.5 The difference of the volume density of capillaries in the white matter was not significant between running group and model control group (P>0.05); the difference of the volume of capillaries in the white matter was significant between running group and model control group (P<0.05); the volume density and volume of capillaries in the white matter between the running group and the vacuity control group were significantly different (P<0.05).2.6 The difference of the surface area density of capillaries in the white matter was not significant between running group and model control group (P>0.05); the difference of the surface area of capillaries in the white matter was significant between running group and model control group (P <0.05); the surface area density and surface area of capillaries in the white matter between the running group and the vacuity control group was significantly different (P<0.05).CONCLUSIONS1. It confirms the conclusion that running exercise has a therapeutic effect on depression.2. This study obtain the change of white matter in depression model of rats as well as the impact of running exercise on capillaries in the white matter through immunohistochemical techniques and stereological means. The basic parameters of the total length, total volume and total surface area of the capillaries in the white matter might provide important dates for future similar studies.3. The changes of the capillaries parameters, which are existed in rats of depression model, can be improved by running exercise. This may be one mechanism of the treatment of depression. |
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