Short-term voluntary exercise enhances the activation of endogenous neural stem cells inintracerebral hemorrhage mice with hyperlipidemia / 西安交通大学学报(医学版)

【Objective】 To investigate the improvement of motor function recovery and the activation of endogenous neural stem cells (eNSCs) via voluntary exercise in mice with hyperlipidemia after intracerebral hemorrhage (ICH). 【Methods】 Four-month-old male Nestin-CreERT2: tdTomato transgenic mice were fed with high-fat diet (HFD) for eight weeks. Type Ⅳ collagenase was micro-injected into the corpus striatum to construct mouse ICH model with the help of stereotaxic apparatus. Voluntary exercise (wheel running) was initiated on the second day after ICH and monitored daily for seven days. Neurological severity score (NSS) and beam walking test were applied to evaluate motor function and coordination. Liver and brain tissues were collected at day 9 after ICH and sliced for staining. Then the Nestin-labeled cells, Ki67+, and doublecortin (DCX)+ in subventricular zone (SVZ) were counted to evaluate eNSCs activation. 【Results】 ① Compared with those of mice fed by chow diet (CD), the body weight, blood glucose level, concentration of lipid metabolism factors and the number of Nile Red positive cells in liver tissue were significantly higher in HFD-fed mice, confirming hyperlipidemia. ② Compared with the sham group, NSS score increased and the distance of cross-beam walking of ICH mice significantly decreased, showing the deficiency of motor function. It could be rescued by 7-day wheel running, as shown by a lower NSS score and a longer cross-beam walking distance. ③ Compared with the sham group, the number of Nestin+/Ki67+ cells decreased and Nestin+/DCX+ cells increased after ICH. After 7-day voluntary exercise, the number of Nestin+/Ki67+ cells decreased but that of Nestin+/DCX+ cells further increased significantly. However, compared with ICH, the increase of Nestin+/DCX+ cells in ICH+Ex was not significant. 【Conclusion】 Short-term voluntary exercise during the acute stage of ICH improved the recovery of motor function and enhance the proliferation of eNSCs in mice with hyperlipidemia. This provides a new idea for further developing ICH accelerated rehabilitation strategy based on eNSCs.

Testosterone Combined with Voluntary Exercise Attenuates Diabetes-induced Pancreatic Apoptosis in Castrated Diabetic Rats Induced by HFD/STZ

Abstract Increased apoptosis in the pancreas and beta cell death causes reduced insulin secretion in type 2 diabetes. This study was aimed to evaluate the effects of exercise training and testosterone administration on apoptosis marker (p53 protein) in the pancreas tissue in animal with diabetes. Type 2 diabetes was induced by high fat diet and injection of low dose STZ (35mg/kg; ip). After 2 months of treatment with testosterone (2mg/kg/day) or voluntary exercise alone or in combination, apoptosis (tunnel assay) and p53 protein (ELISA method) were measured. Testosterone and exercise decreased the blood glucose, HbA1c levels, HOMA-IR, p53 protein expression and increased insulin level in treated diabetic and diabetic castrated groups. Simultaneous treatment of these groups with testosterone together voluntary exercise had an additive effect on reducing p53 expression, blood glucose, HbA1c levels, HOMA-IR and subsequently decreasing apoptosis. Our results suggest that the apoptosis decreasing effect of testosterone and voluntary exercise is associated with the reduced levels of blood glucose, HbA1c and HOMA-IR that subsequently decreased the expression of p53 level.

Voluntary exercise prior to traumatic brain injury alters miRNA expression in the injured mouse cerebral cortex

MicroRNAs (miRNAs) may be important mediators of the profound molecular and cellular changes that occur after traumatic brain injury (TBI). However, the changes and possible roles of miRNAs induced by voluntary exercise prior to TBI are still not known. In this report, the microarray method was used to demonstrate alterations in miRNA expression levels in the cerebral cortex of TBI mice that were pretrained on a running wheel (RW). Voluntary RW exercise prior to TBI: i) significantly decreased the mortality rate and improved the recovery of the righting reflex in TBI mice, and ii) differentially changed the levels of several miRNAs, upregulating some and downregulating others. Furthermore, we revealed global upregulation of miR-21, miR-92a, and miR-874 and downregulation of miR-138, let-7c, and miR-124 expression among the sham-non-runner, TBI-non-runner, and TBI-runner groups. Quantitative reverse transcription polymerase chain reaction data (RT-qPCR) indicated good consistency with the microarray results. Our microarray-based analysis of miRNA expression in mice cerebral cortex after TBI revealed that some miRNAs such as miR-21, miR-92a, miR-874, miR-138, let-7c, and miR-124 could be involved in the prevention and protection afforded by voluntary exercise in a TBI model.

Effects of habitual exercise and diet restriction on the hepatic fat accumulation in Zucker fatty rats / 体力科学

We investigated the effects of habitual exercise and diet restriction on the hepatic fat accumulation in Zucker fatty rats. Male 6-week-old Zucker fatty rats were divided into obese (Ob), diet restriction (DR), and diet restriction + exercise (DR + Ex) groups. Male Zucker lean rats (L) were used as a control group. The rats in the L and Ob groups were maintained on ad libitum diets. The rats in the DR and DR + Ex groups were fed a 30% restricted diet. The rats in the DR + Ex group exercised voluntarily on a wheel ergometer. After 6 weeks of intervention, the serum free fatty acid and leptin levels in the Ob group were significantly higher than those in the L group. In the Ob group, the hepatic triglyceride content was higher than that in the L group and hepatocyte fat infiltration was observed on haematoxylin and eosin staining. These changes were suppressed by DR + Ex, but not by the DR intervention. These results suggest that habitual exercise inhibits fat accumulation in the liver of Zucker fatty rats.

Correlative Changes of Endothelial Nitric Oxide Synthase and Choline Acetyltransferase in the Hippocampus after Exercise / 대한해부학회지

We found that the expression and activity of endothelial nitric oxide synthase (eNOS) is increased in the hippocampus during exercise (Moon et al., 2006). However, the upstream regulatory factor on the eNOS expression in the hippocampus during exercise has not been clear. In this study, we investigate the role of acetylcholine (ACh) as a regulatory factor for the eNOS expression and activity in the hippocampus during exercise. The results of the present study demonstrate that voluntary wheel running exercise for two weeks increases the expression and activity eNOS. In addition, choline acetyltransferase (ChAT) immnunoreacitvity within the hippocampus was increased after 2 weeks exercise. We further found that the upregulation of ACh with treatment of physostigmine, a booster of ACh releasing, increase the expression and activity of eNOS in the hippocampus. This present study provides the evidence that the upregulation of eNOS during exercise may be mediated by ACh in the hippocampus.

Induction of Striatal Neurogenesis by Voluntary Exercise and Environmental Enrichment

OBJECTIVE: To investigate that neurogenesis in the subventricular zone (SVZ), which is already known as neurogenic area where neural stem/progenitor cells persist, and the striatum, which is non-neurogenic area, might be induced by voluntary exercise (VEx) or environmental enrichment (EE), and compare the extent of the neurogenesis with untreated controls. METHOD: Total 12 C57BL/6 mice, 2~3 months old, were recruited as follows; voluntary wheel runner, EE and control. For 2 weeks, VEx group was housed in rat cage (48x26 cm) with 2 running wheels with 3~4 animals/cage, and EE group was housed in the living condition of huge cage (86x76 cm), social interaction (13~14 mice/cage) and objects such as toys, tunnels and running wheel, whereas control group was placed in the standard cage (30x18 cm). RESULTS: VEx and EE tended to increase the densities of mitotic marker BrdU+ cells in SVZ and striatum. They also exhibited more BrdU+ cells (/mm3) into the striatum, even though they did not show statistical significance. Moreover, EE group showed significant increment of the newly generated neurons coexpressed with BrdU+ and betaIII-tubulin+ (/mm3) in SVZ and striatum as compared to those of controls. CONCLUSION: Voluntary physical exercise and EE induced cell proliferation and neurogenesis in both SVZ and striatum. Characteristically, EE could significantly induce neurogenesis in striatum, non-neurogenic area as well as SVZ, typical neurogenic area. Therefore, this strategy might be used to activate neural regeneration in various central nervous system diseases.

VARIOUS IN RUNNING PATTERN AND SKELETAL MUSCLE ADAPTATIONS IN VOLUNTARY RUNNING RATS AT DIFFERENT LOAD / 体力科学

The running behavior and muscle characteristics associated with voluntary running activity were studied in female Fischer 344 rats after 9 weeks of training in voluntary exercise wheel cages. The exercise wheel employed allowed a load to be added to the wheel axis. The running activity was recorded as the number of rotations every 10 s for 24 h, and the number of running bouts, running duration, running speed and distance run per day were varied. Addition of a load to the wheel axis allowed the running style to be changed, and reduced the running duration and speed in each bout. The voluntary running training was done with no load, 30% per body weight load, and 60% per body weight load, and as treadmill running (40 m/min, 60 min/day) .<BR>In the voluntary training, a difference in the total running distance was observed with increased load. The total distance run under 0%, 30% and 60% load in the voluntary group was about 552, 475, and 438 km, respectively, after training for 9 weeks. As a result of training, the weights of dorsiflexor muscles tended to increase with treadmill running, whereas weights of plantar-flexor muscles increased significantly in the voluntary training groups. In the plantaris muscle, the cross-sectional area of all fiber types was not changed by treadmill training, but in voluntary training, almost every type of fiber was enlarged. Voluntary running with a 30% load increased the cross-sectional area of type I and type ha fibers in the plantaris muscle compared with no load exercise. However, no significant differences in the cross-sectional area of these fibers were observed between 30% and 60% load exercise. The fatigue tolerance of the plantaris muscle improved significantly in all training groups, and the 60% load group showed the highest value.<BR>These results suggest that voluntary loaded running is more effective for muscle enlargement than treadmill training and/or voluntary training with no load.

Chronic effects of voluntary exercise on SRBC-induced host defense reactions in rats / 体力科学

A study was conducted to evaluate the chronic effects of regular physical activity on nonspecific and specific immune responses. Male Fischer rats (SPF) exercised voluntarily on running wheels for 4 months, and were then injected intraperitoneally with sheep red blood cells (SRBC), followed by measurement of the host defense functions at -2 d, 3h, 24h and 4 d of antigen stimulation. The following results were obtained:<BR>1) The ability of circulating neutrophils to produce superoxide measured by the spontaneous NBT test showed an earlier and higher (p<0.05) rise after SRBC injection in the exercise group, suggesting that neutrophils were activated <I>in vivo</I> more promptly against foreign-body invasion. This might reflect a priming response of neutrophils at the early phase of SRBC-induced host defense reactions modulated by the previous regular exercise.<BR>2) The ability of neutrophils to produce superoxide in response to <I>in vitro</I> stimulation with <I>Staphylococcus aureus</I> 209 P was markedly reduced during inflammatory response in the sedentary group, whereas that in the exercise group was maintained at a constant level. The value at 4 d after SRBC injection in the sedentary group was decreased to more than 20% below the baseline (p<0.02) . In addition, a significantly (p<0.02) lower value than that in the exercise group was shown, although phagocytic activity was similar in the two groups. This suggested that neutrophil bactericidal activity was decreased in the sedentary group.<BR>3) Plasma IgG levels in the exercise group were consistently and significantly (p<0.0001) higher by about 30% than those in the sedentary group, regardless of SRBC injection. This suggested an enhanced host defense status by regular exercise.<BR>4) The specific humoral immune response to SRBC injection was assessed in terms of hemagglutination and plasma IgM levels, but no significant differences were shown between the groups.

The effect of voluntary exercise and the influence of saline loading on systolic blood pressure and vascular lesions in stroke-prone SHR / 体力科学

The effects of voluntary exercise on resting systolic blood pressure and vascular lesions of stroke-prone spontaneously hypertensive rats (stroke-prone SHR) were investigated with and without 1 % saline loading. Forty male stroke-prone SHR aged 7 weeks were assigned to one of 4 experimental groups. Each consisted 10 animals ; sedentary control (S), sedentary with 1 % saline loading (SS), exercised control (E), and exercised with 1 % saline loading (ES) . Animals were sacrificed at the 5 th week. In the prehypertensive phase, resting caudal arterial systolic blood pressure was significantly lower in the E group than in the S group. However, after being loaded with 1 % saline, the ES group showed higher resting systolic blood pressure than those of the SS group. In addition, the ES group revealed severer renal, myocardial, and cerebrovascular lesions than those of the rest of the groups.

Exercise hyperemia on hindlimb muscles in anesthetized spontaneously hypertensive rats / 体力科学

Muscle blood flows by means of hydrogen gas clearance method were measured on hindlimb muscles in sedentary control (nE) and exercised (Ex) spontaneously hypertensive rats (SHR) . SHR and Wistar control rats (WCR) were divided into two groups at 7 weeks of age ; SHRnE, SHREx and WCRnE, WCREx. Exercised rats were bred in cages with rotating wheels capable of running voluntarily for additional 10 weeks. Body weights of exercised groups in both SHR and WCR were lower than those of sedentary controls, whereas food consumptions of exercised rats tended to be more than those of sedentary controls. Ratios of the heart weight to the body weight of SHR and WCR were higher in exercised groups. There was no significant difference in systolic blood pressure obtained by an indirect tail-cuff method between exercised and sedentary control SHR. Resting blood flows in both M. Gastrocnemius and M. Soleus showed lower values in SHR groups than those in WCR groups. Postexercise blood flows at 1 Hz and 5 Hz were higher in exercised groups. These results suggest that peripheral adaptability of blood flow control to the exercise is still normal on hindlimb muscles in SHR.