Alzheimer disease (AD) is a most common form of dementia and eventually causes impairments of learning ability and memory function. In the present study, we investigated the effects of treadmill exercise on the symptoms of AD focusing on the microglial activation-induced apoptosis. AD was made by bilateral intracerebroventricular injection of streptozotocin. The rats in the exercise groups were made to run on a treadmill once a day for 30 min during 4 weeks. The distance and latency in the Morris water maze task and the latency in the step-down avoidance task were increased in the AD rats, in contrast, treadmill exercise shortened these parameters. The numbers of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive and caspase-3-positive cells in the hippocampal dentate gyrus were decreased in the AD rats, in contrast, treadmill exercise suppressed these numbers. Expressions of glial fibrillary acidic protein (GFAP) and cluster of differentiation molecule 11B (CD11b) in the hippocampal dentate gyrus were increased in the AD rats, in contrast, treadmill exercise suppressed GFAP and CD11b expressions. Bax expression was increased and Bcl-2 expression was decreased in the hippocampus of AD rats, in contrast, treadmill exercise decreased Bax expression and increased Bcl-2 expression. The present results demonstrated that treadmill exercise ameliorated AD-induced impairments of spatial learning ability and short-term memory through suppressing apoptosis. The antiapoptotic effect of treadmill exercise might be ascribed to the inhibitory effect of treadmill exercise on microglial activation.

AIMS:Treadmill exercise is a beneficial treatment following childhood stroke. Thus, studies focusing on the neuroprotective mechanism of exercise training during postischemic treatment in children with ischemic stroke are urgently needed. We evaluated the effects of treadmill exercise on autophagy after cerebral ischemia in young rats.

MAIN METHODS:Rats (23-25 days old) underwent cerebral ischemia-reperfusion (CI/R) surgery. The experimental animals were divided into 5 groups, and some groups received either treadmill exercise, a rapamycin (RAPA) injection or combination therapy for 3 or 7 days. We performed a series of experimental tests including neurological scoring, hematoxylin-eosin staining (H&E), Nissl staining, triphenyl tetrazolium chloride (TTC) staining, Western blot analysis (WB), immunofluorescence (IF), enzyme-linked immunosorbent assay (ELISA), transmission electron microscopy (TEM) and Terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) fluorescence.

KEY FINDINGS:The experimental data indicated that treadmill exercise inhibited autophagy in the ischemic penumbra, inhibited high mobility group box 1 (HMGB1) translocation and binding to Beclin1, reduced apoptosis, reduced infarct volumes, and aided in functional recovery. However, RAPA promoted the opposite effects of treadmill exercise.

SIGNIFICANCE:We found that treadmill exercise improves the neurological deficits induced by CI/R by inhibiting autophagy and HMGB1 binding to Beclin1.

BACKGROUND:Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by polyglutamine (CAG) expansion in the Huntingtin (HTT) gene. The CAGknock-in (KI) mouse model recapitulates the progression of motor symptoms emerging at 12 months of age.

OBJECTIVE:This study was aimed at assessing the effects of exercise, in the form of treadmill running, and examining its impact on motor behavior and markers of metabolism in the CAGKI mouse model of HD after motor symptoms have emerged.

METHODS:CAGKI mice at 13-15 months of age were subjected to treadmill exercise 3 days per week for 1 h per day or remained sedentary. After 12 weeks of exercise brain tissues were analyzed for enzymatic activity including mitochondria Complexes I, II/III, and IV, transglutaminase, aconitase, pyruvate dehydrogenase, and phosphofructokinase1/2. In addition, the concentration was determined for nitrate/nitrite, pyruvate carboxylase, NAD/NADH, and glutamate as well as the ratio of mitochondria and nuclear DNA. Motor behavior was tested using the rotarod.

RESULTS:Exercise resulted in increased [nitrite + nitrate] levels (surmised as nitric oxide), reduced transglutaminase activity, increased aconitase activity with increased tricarboxylic acid-generated reducing equivalents and mitochondrial oxidative phosphorylation complexes activity. Mitochondrial function was strengthened by increases in glycolysis, pyruvate dehydrogenase activity, and anaplerosis component represented by pyruvate carboxylase.

CONCLUSIONS:These changes in mitochondrial function were associated with improved motor performance on the rotarod test. These findings suggest that exercise may have beneficial effects on motor behavior by reversing deficits in mitochondrial function in a rodent model of HD.

Studies demonstrate that asthma, especially during childhood, affects the functions of the brain including learning and memory. Exercise is well known for its neuroprotective functions and for its beneficial effects on asthma. We aimed to assess the effects of exercise on cognitive function, synaptic plasticity, and hippocampal brain-derived neurotrophic factor (BDNF) levels in ovalbumin (OVA) sensitized juvenile rats. Rats were sensitized by intraperitoneal administration and inhaled OVA. Animals were subjected to treadmill running exercise during the OVA-challenged period. T-helper type 2 (Th2) cytokine [interleukin (IL)-4], Th1 cytokine (INF-γ) levels, and INF-γ/IL-4 (Th1/Th2) ratio in bronchoalveolar lavage fluid (BALF), and tracheal response to methacholine and OVA were measured. Further, memory behaviors and BDNF levels were measured in the hippocampus as well as long-term potentiation (LTP) was assessed by recording field excitatory postsynaptic potentials (fEPSPs) in the hippocampus. The levels of IL-4 and TGF-β were decreased but INF-γ level and INF-γ/IL-4 ratio increased in the BALF due to exercise in the OVA-sensitized animals. In addition, exercise improved OVA-sensitization induced cognitive impairments, increased BDNF levels, and enhanced hippocampal LTP in OVA-sensitized rats. Exercise is not only effective in the alleviation of airway inflammation by restoring Th1/Th2 cytokines balance, but also is a candidate for improvement of memory and synaptic plasticity deficits partially through increasing the levelsof hippocampal BDNF in OVA-sensitized rats.

OBJECTIVES:To determine the effects of treadmill exercise training and rutin intervention independently and in combination on key molecules involved in Alzheimer's disease (AD) pathology and cognitive function in diet induced obese (DIO) mice.

METHODS:C57BL/6J mice were randomized into 5 groups: chow group, high fat diet group (HFD), HFD plus rutin intervention group (HR), HFD combined with treadmill running group (HE), HFD combined with treadmill running and rutin group (HRE). At the end of the intervention, Morris water maze test was conducted to assess hippocampal dependent, long term spatial learning and memory retention. Hippocampus and cortex were dissected and the protein expression of key molecules including insulin-degrading enzyme (IDE), Beta-secretase (BACE1), signal transducer and activator of transcription 3 (STAT3), cAMP-response element binding protein (CREB), post-synaptic density protein 95 (PSD-95) and synaptophysin were measured via western blotting.

RESULTS:Exercise and rutin enhances HFD induced cognitive deficits in DIO mice. In the hippocampus, although HFD has no effect on IDE, BACE1, phosphorylation (p)-STAT3 and p-CREB, HR and HE group have elevated protein expression of IDE; meanwhile, p-CREB was elevated in the HE and HRE group. In the cortex, HFD led to induction in BACE1 and reduction in p-STAT3 and PSD95. Rutin or exercise reversed BACE1, p-STAT3 and PSD95 to normal levels.

CONCLUSIONS:Treadmill running and rutin could improve HFD induced cognitive impairment, and p-STAT3, p-CREB, BACE1, IDE, and PSD95 are potential mediators involved in the protective effects of rutin or exercise against HFD induced cognitive dysfunction.

The potential efficacy of fresh turmeric (Curcuma longa) paste to heal wounds was tested in a preclinical study in an animal model. Turmeric paste was compared with honey as a topical medicament against a control on experimentally created full-thickness circular wounds in 18 rabbits (Oryctolagous cuniculus). Wound healing was assessed on the basis of physical, histomorphological, and histochemical parameters on treatment days 0, 3, 7, and 14. Only tensile strength was measured on day 14 of treatment. It was observed that the wound healing was statistically significantly faster (P < .01) in both treatment groups compared to the control group.

We have previously shown that voluntary wheel running (VWR) attenuates, whereas forced treadmill running (FTR) exacerbates, intestinal inflammation and clinical outcomes in a mouse model of colitis. As the gut microbiome is implicated in colitis, we hypothesized that VWR and FTR would differentially affect the gut microbiome. Mice (9-10/treatment) were randomly assigned to VWR, FTR, or sedentary home cage control (SED) for 6 wk. VWR were given running wheel access, whereas FTR ran on a treadmill for 40 min/day at 8-12 m/min, 5% grade. Forty-eight hours after the last exercise session, DNA was isolated from the fecal pellets and cecal contents, and the conserved bacterial 16S rRNA gene was amplified and sequenced using the Illumina Miseq platform. Permutational multivariate analysis of variance based on weighted UniFrac distance matrix revealed different bacterial clusters between feces and cecal contents in all groups (P<0.01). Interestingly, the community structures of the three treatment groups clustered separately from each other in both gut regions (P<0.05). Contrary to our hypothesis, theα-diversity metric, Chao1, indicated that VWR led to reduced bacterial richness compared with FTR or SED (P<0.05). Taxonomic evaluation revealed that both VWR and FTR altered many individual bacterial taxa. Of particular interest, Turicibacter spp., which has been strongly associated with immune function and bowel disease, was significantly lower in VWR vs. SED/FTR. These data indicate that VWR and FTR differentially alter the intestinal microbiome of mice. These effects were observed in both the feces and cecum despite vastly different community structures between each intestinal region.

Obesity increases inflammation, both peripherally and centrally, and exercise can ameliorate some of the negative health outcomes associated with obesity. Within the brain, the effect of obesity on inflammation has been well characterized in the hypothalamus and hippocampus, but has been relatively understudied in other brain regions. The current study was designed to address two primary questions; (1) whether western diet (high fat/high sucrose) consumption would increase markers of inflammation in the prefrontal cortex and (2) whether concurrent voluntary wheel running would ameliorate any inflammation. Adult male mice were exposed to a western diet or a control diet for 8 weeks. Concurrently, half the animals were given running wheels in their home cages, while half did not have access to wheels. At the conclusion of the study, prefrontal cortex was removed and expression of 18 proinflammatory genes was assayed. Expression of a number of proinflammatory molecules was upregulated by consumption of the western diet. For two chemokines, chemokine (C-C motif) ligand 2 (CCL2) and C-X-C motif chemokine 10(CXCL10), voluntary exercise blocked the increase in the expression of these genes. Cluster analysis confirmed that the majority of the tested genes were upregulated by western diet, and identified another small cluster of genes that were downregulated by either diet or exercise. These data identify a proinflammatory phenotype within the prefrontal cortex of mice fed a western diet, and indicate that chemokine induction can be blocked by voluntary exercise.

Obesity is a risk factor for several cardiovascular and metabolic diseases. Its influence on the skin is less obvious, yet certain negative effects of adipose tissue inflammation on the dermis have been suggested. Excess weight is closely associated with sedentary behavior, so any increase in physical activity is considered beneficial against obesity. To investigate the effects of obesity and physical exercise on the skin, we established a mouse model in which mice were kept either on a high-fat diet or received standard chow. After the two groups achieved a significant weight difference, physical exercise was introduced to both. Animals were given the opportunity to perform voluntary exercise for 40 min daily in a hamster wheel for a period of 8 weeks. We evaluated the status of the dermis at the beginning and at the end of the exercise period by in vivo nonlinear microscopy. Obese mice kept on high-fat diet lost weight steadily after they started to exercise. In the high-fat diet group, we could detect significantly larger adipocytes and a thicker layer of subcutaneous tissue; both changes started to normalize after exercise. Nonlinear microscopy revealed an impaired collagen structure in obese mice that improved considerably after physical activity was introduced. With the ability todetect damage on collagen structure, we set out to address the question whether this process is reversible. With the use of a novel imaging method, we were able to show the reversibility of connective tissue deterioration as a benefit of physical exercise.

The molecular mechanisms behind the obesity-breast cancer association may be regulated via adipokine secretion by white adipose tissue. Specifically, adiponectin (ADIPO) and leptin (LEP) are altered with adiposity and exert antagonistic effects on cancer cell proliferation. We set out to determine whether altering adiposity in-vivo via high fat diet (HFD) feeding changed the tumor growth supporting nature of adipose tissue and if voluntary physical activity (VPA) could ameliorate these HFD-dependent effects. We show that conditioned media (CM) created from the adipose tissue of HFD fed animals caused an increase in the proliferation of MCF7 cells compared to cells exposed to CM prepared from the adipose of lean chow diet fed counterparts. This increased proliferation was driven within the MCF7 cells by an HFD-dependent antagonism between AMPK and Akt signaling pathways, decreasing p27 protein levels via reduced phosphorylation at T198 and downregulation of AdiporR1. VPA can ameliorate these proliferative effects of HFD-CM on MCF7 cells, increasing p27(T198) by AMPK, reducing pAkt(T308) and increasing AdipoR1, resulting in cell cycle withdrawal in a manner that depends on the VPA intensity. High physical activity (>3 km/day) completely abolished the effects of HFD feeding. In addition, AdipoR1 overexpression mimics the effects of exercise, abolishing the proliferative effects of the HFD-CM on MCF7 cells and further enhancing the anti-proliferative effects physical activity on the HFD-CM. Thus, VPA represents a means to counteract the proliferative effects of adipose tissue on breast cancers in obese patients.

Exercise has been shown to be protective against the risk of dementias, including Alzheimer's disease (AD). Intervention studies have demonstrated its ability to mitigate cognitive and behavioral impairments and reduce disease in both humans and animals. However, information is lacking in regard to the volume and intensity, as well as timing of exercise onset with respect to disease stage, which produces optimal benefits. Here, utilizing the Tg2576 mouse, a model of AD-like parenchymal amyloid pathology and cognitive impairment, we sought to understand the effects of different lengths of daily access to a running wheel on advanced stage disease. This study is the first to determine the benefits of long-term exercise (4 months of voluntary running) and different periods of daily access to a running wheel (0 h, 1 h, 3 h, and 12 h running wheel access) beginning in 14-month-old Tg2576 mice, an age with significant amyloid pathology. We found that exercising Tg2576 animals showed lower levels of some aspects of AD pathology and reduced behavioral dysfunction compared to sedentary Tg2576 animals.High intensity exercise, rather than high volume exercise, was generally most beneficial in reducing amyloid pathology. Our results suggest that engaging in vigorous exercise programs, even after living a sedentary life, may lead to a measurable reduction in AD pathology and preservation of some cognitive abilities.

PURPOSE:The objective of this study is to verify the beneficial effects of whey protein (WP) supplementation on health promotion and enhance exercise performance in an aerobic-exercise training protocol.

METHODS:In total, 40 male Institute of Cancer Research mice (4 wk old) were divided into four groups (n = 10 per group): sedentary control with vehicle (SC) or WP supplementation (4.1 g·kg, SC + WP), and exercise training with vehicle (ET) or WP supplementation (4.1 g·kg, ET + WP). Animals in the ET and ET + WP groups underwent swimming endurance training for 6 wk, 5 d·wk. Exercise performance was evaluated by forelimb grip strength and exhaustive swimming time as well as by changes in body composition and biochemical parameters at the end of the experiment.

RESULTS:ET significantly decreased final body and muscle weight and levels of albumin, total protein, blood urea nitrogen, creatinine, total cholesterol, and triacylglycerol. ET significantly increased grip strength; relative weight (%) of liver, heart, and brown adipose tissue (BAT); and levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, creatine kinase, and total bilirubin. WP supplementation significantly decreased final body, muscle, liver, BAT, and kidney weight and relative weight (%) of muscle, liver, and BAT as well as levels of aspartate aminotransferase, lactate dehydrogenase, creatine kinase, and uric acid. In addition, WP supplementation slightly increased endurance time and significantly increased grip strength and levels of albumin and total protein.

CONCLUSION:WP supplementation improved exercise performance, body composition, and biochemical assessments in mice and may be an effective ergogenic aid in aerobic exercise training.

OBJECTIVE: To evaluate the wound healing activity of M. recutita (chamomile) extract in rats. METHOD: Wound healing activity was determined using excision, incision and dead space wound models.The animals were divided into two groups of six for each model: animals in the test group were treated with the aqueous extract of M. recutita (120mg/kg/day), which was mixed in their drinking water. Animals in the control group were maintained with plain drinking water. Healing was assessed by the rate of wound contraction, period of epithelialisation, wound-breaking strength, granulation tissue weight and hydoxyproline content.Antimicrobial activity of the extract against various microorganisms was assessed. RESULTS: On day 15 animals in the test group exhibited a greater reduction in the wound area when compared with the controls (61 % versus 48%), faster epithelialisation and a significantly higher wound-breaking strength (p<0.002). In addition, wet and dry granulation tissue weight and hydroxyproline content were significantly higher. CONCLUSION: The increased rate of wound contraction, together with the increased wound-breaking strength, hydroxyproline content and histological observations, support the use of M. recutita in wound management. However, this needs to be studied further before it can be considered for clinical use.