Intra- and Intertumoral Microglia/Macrophage Infiltration and Their Associated Molecular Signature Is Highly Variable in Canine Oligodendroglioma: A Preliminary Evaluation.

The goal of this study was to define the glioma-associated microglia/macrophage (GAM) response and associated molecular landscape in canine oligodendrogliomas. Here, we quantified the intratumoral GAM density of low- and high-grade oligodendrogliomas compared to that of a normal brain, as well as the intratumoral concentration of several known GAM-derived pro-tumorigenic molecules in high-grade oligodendrogliomas compared to that in a normal brain. Our analysis demonstrated marked intra- and intertumoral heterogeneity of GAM infiltration.

Microglia-Derived Olfactomedin-like 3 Is a Potent Angiogenic Factor in Primary Mouse Brain Endothelial Cells: A Novel Target for Glioblastoma.

Neoangiogenesis, a hallmark feature of all malignancies, is robust in glioblastoma (GBM). Vascular endothelial growth factor (VEGF) has long been regarded as the primary pro-angiogenic molecule in GBM. However, anti-VEGF therapies have had little clinical efficacy, highlighting the need to explore VEGF-independent mechanisms of neoangiogenesis.

Prevalence and Clinicopathologic Features of Canine Metastatic Melanoma Involving the Central Nervous System: A Retrospective Analysis and Comparative Review.

Background: Central nervous system (CNS) involvement is the leading cause of death in malignant melanoma. Rodent models, while vital to mechanistic investigation, have had limited success identifying effective therapies for melanoma brain metastases. The companion dog with melanoma is a promising complementary model for developmental therapeutic investigation, as these tumors occur in an immunologically outbred host that has shared environmental exposures with humans.

Microglia-Derived Olfactomedin-like 3 Promotes Pro-Tumorigenic Microglial Function and Malignant Features of Glioma Cells.

Under the influence of transforming growth factor-beta (TGFβ), glioma-associated microglia produce molecules that promote glioma growth and invasion. Olfactomedin-like 3 (), a novel, secreted glycoprotein, is known to promote several non-CNS cancers. While it is a direct TGFβ1 target gene in microglia, the role of microglia-derived OLFML3 in glioma progression is unknown.

Five months of voluntary wheel running downregulates skeletal muscle LINE-1 gene expression in rats.

Transposable elements (TEs) are mobile DNA and constitute approximately half of the human genome. LINE-1 (L1) is the only active autonomous TE in the mammalian genome and has been implicated in a number of diseases as well as aging. We have previously reported that skeletal muscle L1 expression is lower following acute and chronic exercise training in humans.

Rats Selectively Bred for High Voluntary Physical Activity Behavior are Not Protected from the Deleterious Metabolic Effects of a Western Diet When Sedentary.

Background: Physical activity and diet are well-established modifiable factors that influence chronic disease risk. We developed a selectively bred, polygenic model for high and low voluntary running (HVR and LVR, respectively) distances. After 8 generations, large differences in running distance were noted.

Comparison of Cardiac miRNA Transcriptomes Induced by Diabetes and Rapamycin Treatment and Identification of a Rapamycin-Associated Cardiac MicroRNA Signature.

Rapamycin (Rap), an inhibitor of mTORC1, reduces obesity and improves lifespan in mice. However, hyperglycemia and lipid disorders are adverse side effects in patients receiving Rap treatment. We previously reported that diabetes induces pansuppression of cardiac cytokines in Zucker obese rats (ZO-C).

Role of Inactivity in Chronic Diseases: Evolutionary Insight and Pathophysiological Mechanisms.

This review proposes that physical inactivity could be considered a behavior selected by evolution for resting, and also selected to be reinforcing in life-threatening situations in which exercise would be dangerous. Underlying the notion are human twin studies and animal selective breeding studies, both of which provide indirect evidence for the existence of genes for physical inactivity. Approximately 86% of the 325 million in the United States (U.

Left ventricle transcriptomic analysis reveals connective tissue accumulation associates with initial age-dependent decline in V̇o2peak from its lifetime apex.

Peak oxygen consumption (V̇o) strongly predicts morbidity and mortality better than other established risk factors, yet mechanisms associated with its age-associated decline are unknown. Our laboratory has shown that V̇o first begins to decrease at the same age of 19-20 wk in both sedentary and wheel-running, female Wistar rats (Toedebusch et al., Physiol Genomics 48: 101-115, 2016).

Loss of Cdk5 function in the nucleus accumbens decreases wheel running and may mediate age-related declines in voluntary physical activity.

Key Points: Physical inactivity, which drastically increases with advancing age, is associated with numerous chronic diseases. The nucleus accumbens (the pleasure and reward 'hub' in the brain) influences wheel running behaviour in rodents. RNA-sequencing and subsequent bioinformatics analysis led us to hypothesize a potential relationship between the regulation of dendritic spine density, the molecules involved in synaptic transmission, and age-related reductions in wheel running.

Rapid Alterations in Perirenal Adipose Tissue Transcriptomic Networks with Cessation of Voluntary Running.

In maturing rats, the growth of abdominal fat is attenuated by voluntary wheel running. After the cessation of running by wheel locking, a rapid increase in adipose tissue growth to a size that is similar to rats that have never run (i.e.

Comparative adaptations in oxidative and glycolytic muscle fibers in a low voluntary wheel running rat model performing three levels of physical activity.

A unique polygenic model of rat physical activity has been recently developed where rats were selected for the trait of low voluntary wheel running. We utilized this model to identify differences in soleus and plantaris muscles of sedentary low voluntary wheel running rats and physically active low voluntary wheel running rats exposed to moderate amounts of treadmill training. Three groups of 28-day-old male Wistar rats were used: (1) rats without a running wheel (SEDENTARY, n = 7), (2) rats housed with a running wheel (WHEEL, n = 7), and (3) rats housed with a running wheel and exercised on the treadmill (5 days/week for 20 min/day at 15.

AMPK agonist AICAR delays the initial decline in lifetime-apex V̇o2 peak, while voluntary wheel running fails to delay its initial decline in female rats.

There has never been an outcome measure for human health more important than peak oxygen consumption (V̇o2 peak), yet little is known regarding the molecular triggers for its lifetime decline with aging. We examined the ability of physical activity or 5 wk of 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) administration to delay the initial aging-induced decline in lifetime-apex V̇o2 peak and potential underlying molecular mechanisms. Experiment 1 consisted of female rats with (RUN) and without (NO RUN) running wheels, while experiment 2 consisted of female nonrunning rats getting the AMPK agonist AICAR (0.

Endurance Exercise and the Regulation of Skeletal Muscle Metabolism.

Almost a half century ago, regular endurance exercise was shown to improve the capacity of skeletal muscle to oxidize substrates to produce ATP for muscle work. Since then, adaptations in skeletal muscle mRNA level were shown to happen with a single bout of exercise. Protein changes occur within days if daily endurance exercise continues.

Reduced metabolic disease risk profile by voluntary wheel running accompanying juvenile Western diet in rats bred for high and low voluntary exercise.

Metabolic disease risk is influenced by genetics and modifiable factors, such as physical activity and diet. Beginning at 6 weeks of age, rats selectively bred for high (HVR) versus low voluntary running distance (LVR) behaviors were housed in a complex design with or without voluntary running wheels being fed either a standard or Western (WD, 42% kcal from fat and added sucrose) diet for 8 weeks. Upon intervention completion, percent body fat, leptin, insulin, and mediobasal hypothalamic mRNAs related to appetite control were assessed.

Mu opioid receptor modulation in the nucleus accumbens lowers voluntary wheel running in rats bred for high running motivation.

The exact role of opioid receptor signaling in mediating voluntary wheel running is unclear. To provide additional understanding, female rats selectively bred for motivation of low (LVR) versus high voluntary running (HVR) behaviors were used. Aims of this study were 1) to identify intrinsic differences in nucleus accumbens (NAc) mRNA expression of opioid-related transcripts and 2) to determine if nightly wheel running is differently influenced by bilateral NAc injections of either the mu-opioid receptor agonist D-Ala2, NMe-Phe4, Glyo5-enkephalin (DAMGO) (0.

Herbal adaptogens combined with protein fractions from bovine colostrum and hen egg yolk reduce liver TNF-α expression and protein carbonylation in Western diet feeding in rats.

Background: We examined if a purported anti-inflammatory supplement (AF) abrogated Western-diet (WD)-induced liver pathology in rats. AF contained: 1) protein concentrates from bovine colostrum and avian egg yolk; 2) herbal adaptogens and antioxidants; and 3) acetyl-L-carnitine.

Methods: Nine month-old male Brown Norway rats were allowed ad libitum access to WD for 41-43 days and randomly assigned to WD + AF feeding twice daily for the last 31-33 days (n = 8), or WD and water-placebo feeding twice daily for the last 31-33 days (n = 8).

Nucleus accumbens neuronal maturation differences in young rats bred for low versus high voluntary running behaviour.

We compared the nucleus accumbens (NAc) transcriptomes of generation 8 (G8), 34-day-old rats selectively bred for low (LVR) versus high voluntary running (HVR) behaviours in rats that never ran (LVR(non-run) and HVR(non-run)), as well as in rats after 6 days of voluntary wheel running (LVR(run) and HVR(run)). In addition, the NAc transcriptome of wild-type Wistar rats was compared. The purpose of this transcriptomics approach was to generate testable hypotheses as to possible NAc features that may be contributing to running motivation differences between lines.

Unique transcriptomic signature of omental adipose tissue in Ossabaw swine: a model of childhood obesity.

To better understand the impact of childhood obesity on intra-abdominal adipose tissue phenotype, a complete transcriptomic analysis using deep RNA-sequencing (RNA-seq) was performed on omental adipose tissue (OMAT) obtained from lean and Western diet-induced obese juvenile Ossabaw swine. Obese animals had 88% greater body mass, 49% greater body fat content, and a 60% increase in OMAT adipocyte area (all P < 0.05) compared with lean pigs.

Comparing serum responses to acute feedings of an extensively hydrolyzed whey protein concentrate versus a native whey protein concentrate in rats: a metabolomics approach.

We examined how gavage feeding extensively hydrolyzed whey protein (WPH) versus a native whey protein concentrate (WPC) transiently affected serum biochemical profiles in rodents. Male Wistar rats (250-300 g) were 8 h fasted and subsequently fed isonitrogenous amounts of WPH or WPC, or remained unfed (control). Animals were sacrificed 15 min, 30 min, and 60 min post-gavage for serum extraction, and serum was analyzed using untargeted global metabolic profiling via gas chromatography/mass spectrometry (MS) and liquid chromatography/MS/MS platforms.

Sudden decrease in physical activity evokes adipocyte hyperplasia in 70- to 77-day-old rats but not 49- to 56-day-old rats.

The cessation of physical activity in rodents and humans initiates obesogenic mechanisms. The overall purpose of the current study was to determine how the cessation of daily physical activity in rats at 49-56 days of age and at 70-77 days of age via wheel lock (WL) affects adipose tissue characteristics. Male Wistar rats began voluntary running at 28 days old and were either killed at 49-56 days old or at 70-77 days old.

Phenotypic and molecular differences between rats selectively bred to voluntarily run high vs. low nightly distances.

The purpose of the present study was to partially phenotype male and female rats from generations 8-10 (G8-G10) that had been selectively bred to possess low (LVR) vs. high voluntary running (HVR) behavior. Over the first 6 days with wheels, 34-day-old G8 male and female LVRs ran shorter distances (P < 0.

Potential clinical translation of juvenile rodent inactivity models to study the onset of childhood obesity.

According to the latest data from the Center for Disease Control and Prevention 17%, or 12.5 million, of children and adolescents aged 2-19 years in the United States are obese. Physical inactivity is designated as one of the actual causes of US deaths and undoubtedly contributes to the obesity epidemic in children and adults.

Postprandial leucine and insulin responses and toxicological effects of a novel whey protein hydrolysate-based supplement in rats.

The purpose of this study was: aim 1) compare insulin and leucine serum responses after feeding a novel hydrolyzed whey protein (WPH)-based supplement versus a whey protein isolate (WPI) in rats during the post-absorptive state, and aim 2) to perform a thorough toxicological analysis on rats that consume different doses of the novel WPH-based supplement over a 30-day period. In male Wistar rats (~250 g, n = 40), serum insulin and leucine concentrations were quantified up to 120 min after one human equivalent dose of a WPI or the WPH-based supplement. In a second cohort of rats (~250 g, n = 20), we examined serum/blood and liver/kidney histopathological markers after 30 days of feeding low (1human equivalent dose), medium (3 doses) and high (6 doses) amounts of the WPH-based supplement.