The interaction effects of aerobic exercise training and vitamin D supplementation on plasma lipid profiles and insulin resistance in ovariectomized rats

Purpose

The purpose of this study was to determine the interaction effects of aerobic exercise training and vitamin D supplementation on indices of obesity and plasma lipid profiles in ovariectomized (OVX) rats.

Methods

Forty female Wistar rats were divided into 5 groups: aerobic training (3 days/week for 8 weeks; AT; n = 8), aerobic training and vitamin D supplementation (OVX + AT + Vit D; n = 8), vitamin D supplementation (OVX + Vit D; n = 8), ovariectomized control (OVX + C, n = 8) and SHAM (n = 8). After blood sampling, visceral fat was taken from the abdominal cavity and weighed immediately. Data was statistically analyzed by One-way ANOVA and Repeated measure ANOVA tests with a 0.05 significance level.

Results

Body weight, visceral fat, BMI and food intake decreased significantly in OVX + AT + Vit D (P < 0.001); whereas these variables increased significantly in OVX + C (P < 0.001) and SHAM (P < 0.023) groups. At the end of two-months of follow-up, we observed significant differences in TC, TG, HDL-C, LDL-C, glucose, insulin, and HOMA-IR in all groups.

Conclusion

It seems that aerobic training with vitamin D, due to the involvement of muscle mass and exposure to dynamic pressure on the bones and muscles, increased energy expenditure, stimulated insulin exudation and glucose homeostasis, decreased insulin resistance and improved the lipid profile in ovariectomized rats.     

Changes of bone metabolism based on the different interventions with exercise type or additional intake material in ovariectomized rats

[Purpose]

This study is aimed at providing clear guidance on treatment and prevention of osteoporosis by comparing and analyzing some well-known methods out of drug and exercise therapies.

[Methods]

For this purpose, eight-week experiments (drug therapy and exercise therapy) were carried out by using rats whose menopause was induced by the removal of an ovary. In the treatment of the drug therapy, the effects of soy protein, one of the well-known alendronate and estrogen replacement therapy, were compared and analyzed. In the treatment of the exercise therapy, endurance exercise using a treadmill and resistance exercise through climbing a special cage were compared and analyzed. Based on these results, this study will be able to suggest the most appropriate way to deal with osteoporosis which requires long-term treatment. Sixty eight-week-old Sprague-Dawley female rats had a week to adapt to the new environment. After that, they were randomly divided into four groups (Sham-Sedentary; SS, ovariectomized-control; OC, ovariectomized-soy protein; OS: ovariectomized-alendronate; OA, ovariectomized-endurance exercise; OE, ovariectomized-resistance exercise; OR) before having an operation for the removal of an ovary. After surgery, the rats convalesced for a week. Alendronate (0.4mg / kg of body weight) and isoflavones (200g / 1 kg of feed) were given to two groups respectively for eight weeks. The rats in the other two groups performed resistance exercise (climbing) and endurance exercise (20 m/min; 60min/day) five days a week for eight weeks.

[Results]

Ovariectomy increased the body weight and body fat like menopause did. Soy protein and alendronate intake for eight weeks had no effect on body weight but reduced the body fat increased by ovariectomy to the level of the SS group. The menopause induced by ovariectomy did not affect total bone density and bone mass as well as bone density in specific areas of the body. Soy protein and alendronate intake for eight weeks did not significantly affect them either. However, the eight-week treatment with soy protein and alendronate significantly reduced the level of osteocalcin in blood. Resistance exercise more noticeably increased body weight and bone mass than running on the low-intensity treadmill but serum osteocalcin levels were notably increased in both cases.

[Conclusion]

These results show that soy protein which is natural produce and low-intensity, regular endurance exercise also have an effect on the treatment and prevention of osteoporosis caused by menopause.     

Effects of skim milk powder intake and treadmill training exercise on renal,bone and metabolic parameters in aged obese rats

Purpose

we aim to examine whether adding exercise has impact on obesity prevention and bone metabolism in senior rats, to which dietary obesity was induced through skim milk intake.

Methods

We used 47, 14-week old Sprague -Dawley (SD) female rats (CLEA Japan, Inc.). The Rats were separated into four random groups: 1) a Non-Ex group with a normal diet (n = 12), 2) an Ex group with a normal diet (n = 12), 3) a Non-Ex group with a skim milk diet (n = 11), and 4) an Ex group with a skim milk diet (n = 12). As the exercise for each Ex group, rats ran on a treadmill starting at 27-week old (TREADMILL CONTROL LE8710 and TREADMILL CONTROL LE8700, Harvard Bioscience). Training protocol stipulated a frequency of five times a week for 12 weeks.

Results

The leptin concentration differed with dietary content: compared to the Ex group with a skim milk diet, Non-Ex and Ex groups with a normal diet showed significantly higher values (p < 0.05). The Ex group had significantly lower values in both the normal diet and skim milk diet groups with or without exercise (p < 0.05). Compared to the Non-Ex group with a normal diet, BS/BV (mm²/mm³), BV/TV (%), Tb.Th (μm), TBPf (/mm) and Tb.N (/mm) had significantly lower in the Ex group, the Ex and Non-Ex groups with a whey protein diet, and the Ex group with a skim milk protein diet (p < 0.05).

Conclusion

These findings suggest that senior female rats fed SMP would have higher bone structural and strength parameters than rats fed a normal diet.     

DHEA administration has limited effect onintestinal Ca absorption in ovariectomized rats

[Purpose]

The effect of dehydroepiandrosterone (DHEA) administration on intestinal Calcium (Ca) absorption in estrogen deficiency state has not been studied yet. We examined the bone mineral content (BMC) of lumbar spine and Ca balance such as intestinal Ca absorption and Ca accumulation in ovariectomized (OVX) rats after 8 weeks of DHEA administration.

[Methods]

Seventeen female Sprague-Dawley rats, 6 weeks old, were randomized into two groups: OVX control rats (OC, n = 8) and OVX rats with DHEA treatment (OD, n = 9). DHEA was administered to the OD group intraperitoneally at 20 mg DHEA/kg body weight for 8 weeks while the OC group was treated with vehicle only.

[Results]

The BMC normalized by body weight of the lumbar spine (trabecular-abundant region) in the OD group was found to be significantly higher compared to that in the OC group. The femoral wet weight normalized by body weight in the OD group was significantly higher compared to that in the OC group. The intestinal Ca absorption, rate of intestinal Ca absorption, Ca accumulation, and rate of Ca accumulation decreased from the 4th and 5th of the experimental diet period to the end of the experimental period, but interaction of time and group was not observed. In both periods, all parameters did not differ between the groups.

[Conclusion]

The present study confirmed the positive effect of DHEA on trabecular bone mass in ovariectomized rats. On the other hand, DHEA administration might have limited the impact on intestinal Ca absorption in estrogen deficiency state.     

The effects of different exercise modes for preventing endothelial dysfunction of arteries and bone loss in ovariectomized rats

[Purpose]

Several epidemiological studies have demonstrated that there are positive correlations between vascular disorders and bone loss in postmenopausal women. The aim of the present study was to examine the effect of different types of exercise (e.g., climbing and swimming) for preventing endothelial dysfunction of arteries and bone loss in ovariectomized rats.

[Methods]

Twenty Sprague-Dawley female rats were randomly divided into three groups: ovariectomy (OVX) plus treatment with vitamin D₃ and nicotine (VDN) (control rats [Con], n = 7), which is an animal model for endothelial dysfunction and bone loss; voluntary climbing resistance exercise with OVX plus VDN (climbing rats [Clim], n = 6), and swimming exercise with OVX plus VDN (swimming rats [Swim], n = 7). The period of exercise training was 8 weeks.

[Results]

The endothelin-1 (ET-1) protein levels were significantly lower in the Clim and Swim groups than in the Con. The endothelial nitric oxide synthase protein levels were significantly higher in the Swim group than in the Con, but they did not differ between the Clim and Con groups. The cortical bone mineral density in the tibia and breaking energy of the femur were significantly higher in the Clim group than in the Con, but this positive effect was not seen in the Swim group.

[Conclusion]

Voluntary climbing exercise decreased arterial ET-1 protein levels and prevented bone loss in a postmenopause-model rat combining OVX and VDN. Conversely, swimming suppressed endothelial dysfunction of the arteries but did not prevent bone loss. Thus, the type of exercise should be cautiously chosen for enhancing vascular function and bone status, especially in females after menopause.     

Effect of electrical stimulation-induced muscle force and streptomycin treatment on muscle and trabecular bone mass in early-stage disuse musculoskeletal atrophy

Objectives:

The aim was to determine whether daily muscle electrical stimulation (ES) and streptomycin treatment would have positive or negative effects on trabecular bone mass in disuse rats.

Methods:

Seven-week-old male F344 rats were randomly divided into five groups of eight animals each: an age-matched control group (CON); a sciatic denervation group (DN); a DN + direct electrical stimulation group (DN+ES); a DN + streptomycin treatment group (DN+SM); and a DN+ES+SM group. The tibialis anterior (TA) muscles in all ES groups were stimulated with 16mA at 10Hz for 30 min/day, six days/week, for one week. Bone volume and structure were evaluated using micro-CT, and histological examinations of the tibiae were performed.

Results:

Direct ES significantly reduced the disuse-induced trabecular bone loss. Osteoid thickness were also significantly greater in the ES groups than in the DN group. Micro CT and histomorphological parameters were significantly lower in the DN+ES+SM group than in the DN+ES group, while there were no significant differences between the DN and DN+SM groups.

Conclusions:

These results suggest that ES-induced muscle force reduced trabecular bone loss, and streptomycin treatment did not induce bone loss, but attenuated the effects of ES-induced muscle force on reducing the loss of disused bone.     

Hemodynamic and Neuropathological Analysis in Rats with Aluminum Trichloride-Induced Alzheimer's Disease

Background and Aims

Hemodynamic normality is crucial to maintaining the integrity of cerebral vessels and, therefore, preserving the cognitive functions of Alzheimer''s disease patients. This study investigates the implications of the hemodynamic changes and the neuropathological diversifications of AlCl₃-induced AD.

Methods

The experimental animals were 8- to 12-wk-old male Wistar rats. The rats were randomly divided into 2 groups: a control group and a (+)control group. Food intake, water intake, and weight changes were recorded daily for 22 wk. Synchronously, the regional cerebral blood flow (rCBF) of the rats with AlCl₃-induced AD were measured using magnetic resonance imaging (MRI). The hemorheological parameters were analyzed using a computerized auto-rotational rheometer. The brain tissue of the subjects was analyzed using immunohistological chemical (IHC) staining to determine the beta-amyloid (Aβ) levels.

Results

The results of hemodynamic analysis revealed that the whole blood viscosity (WBV), fibrinogen, plasma viscosity and RBC aggregation index (RAI) in (+)control were significantly higher than that of control group, while erythrocyte electrophoresis (EI) of whole blood in (+)control were significantly lower than that of control group. The results of acetylcholinesterase-RBC (AChE-RBC)in the (+)control group was significantly higher than that of the control group. The results also show that the reduction of rCBF in rats with AlCl₃-induced AD was approximately 50% to 60% that of normal rats. IHC stain results show that significantly more Aβ plaques accumulated in the hippocampus and cortex of the (+)control than in the control group.

Conclusion

The results accentuate the importance of hemorheology and reinforce the specific association between hemodynamic and neuropathological changes in rats with AlCl₃-induced AD. Hemorheological parameters, such as WBV and fibrinogen, and AChE-RBC were ultimately proven to be useful biomarkers of the severity and progression of AD patients. In addition, the parameters can be substituted for invasive inspection in therapeutic intervention.     

Comparative effects of alendronate and alfacalcidol on cancellous and cortical bone mass and bone mechanical properties in ovariectomized rats.

The purpose of the present study was to compare the effects of alendronate and alfacalcidol on cancellous and cortical bone mass and bone mechanical properties in ovariectomized rats. Twenty-six female Sprague-Dawley rats, 7 months of age, were randomized by the stratified weight method into four groups: the sham-operated control (Sham) group and the three ovariectomy (OVX) groups, namely, OVX + vehicle, OVX + alendronate (2.5 mg/kg, p.o., daily), and OVX + alfacalcidol (0.5 mug/kg, p.o., daily). At the end of the 8-week experimental period, bone histomorphometric analyses of cancellous bone at the proximal tibial metaphysis and cortical bone at the tibial diaphysis were performed, and the mechanical properties of the femoral distal metaphysis and femoral diaphysis were evaluated. OVX decreased cancellous bone volume per total tissue volume (BV/TV), and the maximum load of the femoral distal metaphysis, as a result of increases in serum osteocalcin (OC) levels, and also the number of osteoclasts (N.Oc), osteoclast surface (OcS) and bone formation rate (BFR) per bone surface (BS), and BFR/BV, without any effect on cortical area (Ct Ar), or maximum load of the femoral diaphysis. Alendronate prevented this decrease in cancellous BV/TV by suppressing increases in N.Oc/BS, OcS/BS, BFR/BS, and BFR/BV, without any apparent effect on Ct Ar, or maximum load of the femoral distal metaphysis and femoral diaphysis. On the other hand, alfacalcidol increased cancellous BV/TV, Ct Ar, and the maximum load of the femoral distal metaphysis and femoral diaphysis, by mildly decreasing trabecular BFR/BV, maintaining trabecular mineral apposition rate and osteoblast surface per BS, increasing periosteal and endocortical BFR/BS, and preventing an increase in endocortical eroded surface per BS. The present study clearly showed the differential skeletal effects of alendronate and alfacalcidol in ovariectomized rats. Alendronate prevented OVX-induced cancellous bone loss by suppressing bone turnover, while alfacalcidol improved cancellous and cortical bone mass and bone strength by suppressing bone resorption and maintaining or even increasing bone formation.     

The Improved Biological Performance of a Novel Low Elastic Modulus Implant

Background

The mismatch of the elastic modulus between implants and bone tissue can lead to stress shielding, bone resorption and poor osseointegration. Compared with normal bone tissue, this problem is much more serious in osteoporosis. The purpose of this study was designed to find out whether the novel Ti-24Nb-4Zr-7.9Sn (TNZS) implant with low elastic modulus and high strength was suitable for biomedical material, especially in osteoporosis.

Methodology

In vitro study, the viability and Alkaline phosphatase (ALP) activity of osteoblasts on the TNZS and Ti-6V-4V (TAV) were observed. In vivo study, 30 adult female New Zealand rabbits were selected and divided randomly into two groups: sham-operation (SHAM, n = 6) and ovariectomised in combination with methylprednisolone treatment (OVX+MP, n = 24). Two implants were then placed in the tibia of each OVX + MP group rabbit, one in each side (left: TAV; right: TNZS). The OVX + MP group rabbits were sacrificed at 4 and 12 weeks after the implantation. The osteoporotic bone responses to the TNZS and TAV implants were evaluated by pull-out test, Micro-CT analyses and histological observation.

Principal Findings

Compared with the TAV group, the TNZS group showed a significant increase (P<0.05) in cell viability and ALP activity, new bone formation and pull-out force.

Conclusions

The novel TNZS implants show good biological performance both in vitro and in vivo, which suggests that the alloys are suitable for biomedical applications, especially in osteoporosis.     

Exercise Training suppresses vascular fibrosis in aging obesity induced rats

[Purpose]

The aim of this study was to investigate the effects of exercise training (ET) on vascular fibrosis in aging model rats with diet-induced obesity.

[Methods]

Twenty-four male Sprague-Dawley rats were divided into 3 groups: Aging control (A-C), A-C with high fat diet (AHF), AHF with ET (AHF + ET). Aging was induced by D-galactose (D-gal) and obesity was induced by HFD (60% fat) for 9 weeks. The experimental rats performed swimming (60 min/day, 5 days/week) for 8 weeks. All rat aorta samples were harvested for RT-PCR and morphologic analyses.

[Results]

The exercise training significantly decreased levels of AT-1, TGF-ß and Coll-1 gene expression compared to AHF group. The AHF + ET group showed a reduced collagen accumulation in the aorta media compared to AHF group.

[Conclusion]

These results suggest that ET could protect the aging obesity aorta against down-regulation of fibrotic factors (AT-1, TGF-ß and Coll-1 gene) and fibrosis by inhibition of collagen accumulation in the aorta media.     

Influence of Mesenchymal Stem Cell Transplantation on Stereotypic Behavior and Dopamine Levels in Rats with Tourette Syndrome

Context

Tourette syndrome (TS) is a heterogeneous neuropsychiatric disorder. Chronic motor and phonic tics are central symptoms in TS patients. For some patients, tics are intractable to any traditional treatment and cause lifelong impairment and life-threatening symptoms. New therapies should be developed to address symptoms and overt manifestations of TS. Transplantation of neurogenic stem cells might be a viable approach in TS treatment.

Objective

We used mesenchymal stem cell (MSC) transplantation to treat TS. We discuss the mechanism of action, as well as the efficiency of this approach, in treating TS.

Settings and Design

An autoimmune TS animal model was adopted in the present study. Forty-eight Wistar rats were randomly allocated to the control group and the 2 experimental groups, namely, TS rats+vehicle and TS rats+MSC. MSCs were co-cultured with 5-bromodeoxyuridine (BrdU) for 24 h for labeling prior to grafting.

Methods

Stereotypic behaviors were recorded at 1, 7, 14, and 28 days after transplantation. Dopamine (DA) content in the striatum of rats in the 3 groups was measured using a high-performance liquid chromatography column equipped with an electrochemical detector (HPLC-ECD) on day 28 after transplantation.

Statistical analysis

Statistical analysis was performed by repeated measurements analysis of variance to evaluate stereotypic behavior counts at different time points.

Results

TS rats exhibited higher stereotypic behavioral counts compared with the control group. One week after transplantation, TS rats with MSC grafts exhibited significantly decreased stereotypic behavior. Rats with MSC grafts also showed reduced levels of DA in the striatum when compared with TS rats, which were exposed only to the vehicle.

Conclusions

Intrastriatal transplantation of MSCs can provide relief from the stereotypic behavior of TS. Our results indicate that this approach may have potential for developing therapies against TS. The mechanism(s) of the observed effect may be related to the suppression of DA system by decreasing the content of DA in TS rats.     

Combined Oral Administration of Bovine Collagen Peptides with Calcium Citrate Inhibits Bone Loss in Ovariectomized Rats

Purpose

Collagen peptides (CPs) and calcium citrate are commonly used as bone health supplements for treating osteoporosis. However, it remains unknown whether the combination of oral bovine CPs with calcium citrate is more effective than administration of either agent alone.

Methods

Forty 12-week-old Sprague-Dawley rats were randomly divided into five groups (n = 8) for once-daily intragastric administration of different treatments for 3 months at 3 months after ovariectomy (OVX) as follows: sham + vehicle; OVX + vehicle; OVX + 750 mg/kg CP; OVX + CP-calcium citrate (75 mg/kg); OVX + calcium citrate (75 mg/kg). After euthanasia, the femurs were removed and analyzed by dual energy X-ray absorptiometry and micro-computed tomography, and serum samples were analyzed for bone metabolic markers.

Results

OVX rats supplemented with CPs or CP-calcium citrate showed osteoprotective effects, with reductions in the OVX-induced decreases in their femoral bone mineral density. Moreover, CP-calcium citrate prevented trabecular bone loss, improved the microarchitecture of the distal femur, and significantly inhibited bone loss with increased bone volume, connectivity density, and trabecular number compared with OVX control rats. CP or CP-calcium citrate administration significantly increased serum procollagen type I N-terminal propeptide levels and reduced serum bone-specific alkaline phosphatase, osteocalcin, and C-telopeptide of type I collagen levels.

Conclusions

Our data indicate that combined oral administration of bovine CPs with calcium citrate inhibits bone loss in OVX rats. The present findings suggest that combined oral administration of bovine CPs with calcium citrate is a promising alternative for reducing bone loss in osteopenic postmenopausal women.     

阿司匹林对去势大鼠腰椎骨密度及微观结构的影响

目的:研究阿司匹林对去势(卵巢切除)大鼠腰椎骨密度及微观结构的影响。方法:取48只3月龄SD雌性大鼠随机分为6组:去势组(OVX组)、对照组(Sham组)及4个阿司匹林治疗组(Aspirin组),每组8只。OVX组及Aspirin组采用卵巢切除法建立骨质疏松模型。去势后1周,阿司匹林治疗组剂量分别为2.25、4.46、8.92及26.75 mg/kg(A1、A2、A3及A4组),每天灌胃一次,OVX组及Sham组予同等量生理盐水灌胃。灌胃3个月后处死,剖取腰椎椎体,以双能X线吸收骨密度测量仪(DXA)和Micro-CT进行测量分析。结果:DXA分析结果显示:阿司匹林各剂量组BMD值较OVX组有统计学差异(P<0.01)。Micro-CT分析表明:与OVX组比较,阿司匹林各剂量组BV/TV、Tb.Th、Tb.N、BMD均显著性提高(P<0.01),BS/BV、Tb.Sp显著性降低(P<0.01),阿司匹林各剂量组BV/TV、BS/BV、Tb.Th、Tb.N、Tb.Sp、BMD与Sham组相比有统计学差异(P<0.01)。结论:阿司匹林可以改善去势大鼠骨小梁结构,增加骨质密度,对去势大鼠骨质疏松具有防治作用,其作用途径可能包括抑制骨吸收和刺激骨形成两方面。     

Reproductive Senescence Blunts Response of Estrogen Receptor-α Expression to Estrogen Treatment in Rat Post-Ischemic Cerebral Microvessels

Background

Several studies demonstrate that estrogen treatment improves cerebral blood flow in ischemic brain regions of young ovariectomized (OVX) rats. Estrogen receptor-α (ER-α) may mediate estrogen’s beneficial actions via its effects on the cerebral microvasculature. However, estrogen-derived benefit may be attenuated in aged, reproductively senescent (RS) rats. Our goal was to determine the effects of aging, estrogen deprivation and estrogen repletion with oral conjugated estrogens (CE) on postischemic cerebral microvascular protein expression of ER-α and ER-β.

Methods

Fisher-344 (n = 37) female rats were randomly divided into the following groups: OVX, OVX CE-treated, RS untreated, and RS CE-treated. After 30 days pretreatment with CE (0.01 mg/kg) rats were subjected to15 min. transient global cerebral ischemia. Non-ischemic naïve, OVX and RS rats were used as controls. Expression of ER-α and ER-β in isolated cortical cerebral microvessels (20 to 100 µm in diameter) was assessed using Western blot and immunohistochemistry techniques.

Results

Age and reproductive status blunted nonischemic ER-α expression in microvessels of OVX rats (0.31±0.05) and RS rats (0.33±0.06) compared to naïve rats (0.45±0.02). Postischemic microvascular expression of ER-α in OVX rats (0.01±0.0) was increased by CE treatment (0.04±0.01). Expression of ER-α in microvessels of RS rats (0.03±0.02) was unaffected by CE treatment (0.01±0.02). Western blot data are presented as a ratio of ER-α or ER-β proteins to β-actin and. Oral CE treatment had no effect on ER-β expression in postischemic microvessels of OVX and RS rats. Statistical analysis was performed by One-Way ANOVA and a Newman-Keuls or Student’s post-hoc test.

Conclusion

Chronic treatment with CE increases ER-α but not ER-β expression in cerebral microvessels of OVX rats. Aging appears to reduce the normal ability of estrogen to increase ER-α expression in postischemic cerebral microvessels.     

Distributional Variations in Trabecular Architecture of the Mandibular Bone: An In Vivo Micro-CT Analysis in Rats

Purpose

To evaluate the effect of trabecular thickness and trabecular separation on modulating the trabecular architecture of the mandibular bone in ovariectomized rats.

Materials and Methods

Fourteen 12-week-old adult female Wistar rats were divided into an ovariectomy group (OVX) and a sham-ovariectomy group (sham). Five months after the surgery, the mandibles from 14 rats (seven OVX and seven sham) were analyzed by micro-CT. Images of inter-radicular alveolar bone of the mandibular first molars underwent three-dimensional reconstruction and were analyzed.

Results

Compared to the sham group, trabecular thickness in OVX alveolar bone decreased by 27% (P = 0.012), but trabecular separation in OVX alveolar bone increased by 59% (P = 0.005). A thickness and separation map showed that trabeculae of less than 100μm increased by 46%, whereas trabeculae of more than 200μm decreased by more than 40% in the OVX group compared to those in the sham group. Furthermore, the OVX separation of those trabecular of more than 200μm was 65% higher compared to the sham group. Bone mineral density (P = 0.028) and bone volume fraction (p = 0.001) were also significantly decreased in the OVX group compared to the sham group.

Conclusions

Ovariectomy-induced bone loss in mandibular bone may be related to the distributional variations in trabecular thickness and separation which profoundly impact the modulation of the trabecular architecture.     

Feeding blueberry diets in early life prevent senescence of osteoblasts and bone loss in ovariectomized adult female rats

Background

Appropriate nutrition during early development is essential for maximal bone mass accretion; however, linkage between early nutrition, childhood bone mass, peak bone mass in adulthood, and prevention of bone loss later in life has not been studied.

Methodology and Principal Findings

In this report, we show that feeding a high quality diet supplemented with blueberries (BB) to pre-pubertal rats throughout development or only between postnatal day 20 (PND20) and PND34 prevented ovariectomy (OVX)-induced bone loss in adult life. This protective effect of BB is due to suppression of osteoblastic cell senescence associated with acute loss of myosin expression after OVX. Early exposure of pre-osteoblasts to serum from BB-fed rats was found to consistently increase myosin expression. This led to maintenance osteoblastic cell development and differentiation and delay of cellular entrance into senescence through regulation of the Runx2 gene. High bone turnover after OVX results in insufficient collagenous matrix support for new osteoblasts and their precursors to express myosin and other cytoskeletal elements required for osteoblast activity and differentiation.

Conclusions/Significance

These results indicate: 1) a significant prevention of OVX-induced bone loss from adult rats can occur with only 14 days consumption of a BB-containing diet immediately prior to puberty; and 2) the molecular mechanisms underlying these effects involves increased myosin production which stimulates osteoblast differentiation and reduces mesenchymal stromal cell senescence.     

动态观察去卵巢骨质疏松大鼠股骨骨微结构的变化

目的:绝经后骨质疏松是好发于中老年女性人群中的骨代谢疾病,去卵巢骨质疏松大鼠模型是国内外通用的模拟绝经后骨质疏松发生的经典动物模型,本研究通过观察去卵巢骨质疏松大鼠股骨骨微结构的动态变化,为骨质疏松大鼠模型的临床应用提供理论参考依据。方法:将90只3月龄雌性SD大鼠按体重分层后随机分为基础组(10只)、假手术组(40只)和去卵巢组(40只)。分别在手术前(基础组)和后的3、6、12、24周,腹主动脉取血处死基础组以及假手术组和去卵巢组大鼠,每组各8-10只。每组中随机取6只大鼠,对其左股骨行micro-CT扫描及三维结构重建。选择股骨远端距生长板远端1 mm处,2.0 mm×3.5 mm,厚0.9 mm的骨组织为感兴趣区域,对感兴趣区域进行骨形态计量学分析。结果:与0周组比较,从去卵巢3周开始一直持续到24周,去卵巢组大鼠股骨vBMD、BV/TV和Tb.N显著降低,Tb.Sp和SMI显著升高,而Tb.Th无显著变化;与0周组比较,从假手术后3周开始一直到24周,假手术组所有检测指标均无显著变化。与同周龄假手术组比较,从去卵巢3周开始一直持续到24周,去卵巢组大鼠股骨Tb.N、BV/TV和vBMD显著降低,Tb.Sp显著升高,而Tb.Th没有显著变化。从去卵巢6周开始一直到24周,去卵巢组大鼠SMI显著增加。结论:3月龄大鼠股骨远端的骨微结构在去卵巢3周时就出现显著变化。提示,采用3月龄大鼠进行抗骨质疏松药物筛选时,去卵巢3周后就可以进行药物处理。     

Effects of long-term resistance exercise training on autophagy in rat skeletal muscle of chloroquine-induced sporadic inclusion body myositis

Purpose

We examined whether resistance exercise training restores impaired autophagy functions caused by Chloroquine (CQ)-induced Sporadic Inclusion Body Myositis (sIBM) in rat skeletal muscle.

Methods

Male wistar rats were randomly assigned into three groups: Sham (n = 6), CQ (n = 6), and CQ + Exercise (CE, n = 6). To create a rat model of sIBM, rats in the CQ and CE group were intraperitoneally injected with CQ 5 days a week for 16 weeks. Rats in the CE group performed resistance exercise training 3 times a week for 8 weeks in conjunction with CQ starting from week 9 to week 16. During the training period, maximal carrying load, body weight, muscle weight, and relative muscle weight were measured. Autophagy responses were examined by measuring specific markers.

Results

While maximal carrying capacity for resistance exercise training was dramatically increased in the CE group, no significant changes occurred in the skeletal muscle weight as well as in the relative muscle weight of CE compared to the other groups. CQ treatment caused significant increases in the levels of Beclin-1 and p62, and decreases in the levels of LAMP-2 proteins. Interestingly, no significant differences in the LC3-II/I ratio or the LC3-II protein levels were observed. Although CQ-treatment groups suppressed the levels of the potent autophagy inducer, BNIP3, p62 levels were decreased in only the CE group.

Conclusion

Our findings demonstrate that sIBM induced by CQ treatment results in muscle degeneration via impaired autophagy and that resistance exercise training improves movable loading activity. Finally, regular exercise training may provide protection against sIBM by enhancing the autophagy flux through p62 protein.     

Adiponectin Alleviates Genioglossal Mitochondrial Dysfunction in Rats Exposed to Intermittent Hypoxia

Background

Genioglossal dysfunction is involved in the pathophysiology of obstructive sleep apnea hypoxia syndrome (OSAHS) characterized by nocturnal chronic intermittent hypoxia (CIH). The pathophysiology of genioglossal dysfunction and possible targeted pharmacotherapy for alleviation of genioglossal injury in CIH require further investigation.

Methodology/Principal Findings

Rats in the control group were exposed to normal air, while rats in the CIH group and CIH+adiponectin (AD) group were exposed to the same CIH condition (CIH 8 hr/day for 5 successive weeks). Furthermore, rats in CIH+AD group were administrated intravenous AD supplementation at the dosage of 10 µg, twice a week for 5 consecutive weeks. We found that CIH-induced genioglossus (GG) injury was correlated with mitochondrial dysfunction, reduction in the numbers of mitochondrias, impaired mitochondrial ultrastructure, and a reduction in type I fibers. Compared with the CIH group, impaired mitochondrial structure and function was significantly improved and a percentage of type I fiber was elevated in the CIH+AD group. Moreover, compared with the control group, the rats’ GG in the CIH group showed a significant decrease in phosphorylation of LKB1, AMPK, and PGC1-α, whereas there was significant rescue of such reduction in phosphorylation within the CIH+AD group.

Conclusions

CIH exposure reduces mitochondrial biogenesis and impairs mitochondrial function in GG, while AD supplementation increases mitochondrial contents and alleviates CIH-induced mitochondrial dysfunction possibly through the AMPK pathway.     

去卵巢大鼠腰椎骨微结构变化的动态观察

目的:动态观察去卵巢大鼠腰椎骨微结构的变化。方法:将90只3月龄雌性SD大鼠按体重进行分层随机抽样分组,分为基础组(10只)、假手术组(40只)和去卵巢组(40只)。手术前(0周)处死基础组大鼠,手术后3、6、12、24周时,分批处死假手术和去卵巢组大鼠各8-10只。从每组随机取6只大鼠的第5腰椎行micro-CT扫描及三维结构重建,选取椎体1 mm处,2.0 mm×3.5mm,厚0.9 mm的骨组织为感兴趣区域(interesting area),进行骨形态计量学分析。结果:与同一时间点假手术组大鼠比较,去卵巢3周时,第5腰椎体积骨密度(v BMD)、骨体积分数(BV/TV)、骨小梁数目(Tb.N)、骨小梁厚度(Tb.Th)、骨小梁间隙(Tb.Sp)和结构模型指数(SMI)均无显著变化;去卵巢6周时,Tb.Th显著下降(P0.05),而其他指标均无显著变化;从去卵巢12周到24周时,不仅Tb.Th显著下降(P0.05),而且v BMD、BV/TV和Tb.N也显著下降(P0.05),同时Tb.Sp和SMI显著增加(P0.05)。结论:3月龄大鼠在去卵巢后的6周时骨小梁厚度变薄,12周以后,体积骨密度和骨体积分数下降,骨小梁数目减少。