Rats selectively-bred for low and high voluntary running: co-selected traits and the effects of voluntary running on the dentate gyrus transcriptome

2014 ◽  
Author(s):  
◽  
Jacob Daniel Brown
Keyword(s):  
Physical Activity ◽  
Locomotor Activity ◽  
Dentate Gyrus ◽  
Selective Breeding ◽  
Drugs Of Abuse ◽  
Wheel Running ◽  
University Of Missouri ◽  
Voluntary Running ◽  
The University ◽  
Physical Activity Motivation

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] The Booth lab at the University of Missouri has selectively-bred Wistar rats for low (LVR) and high (HVR) voluntary running behavior as a model for examining the genetic and physiological origins of physical activity motivation. The major advantage of selective breeding over non-natural methods of genetic engineering is the perpetuation of naturally-existing, polygenic milieus that dictate complex behaviors or phenotypes (e.g. motivation to be physically active, etiology of obesity). Since most genes and physiological systems are pleiotropic and function as modular networks, a "by-product" of selective breeding is the co-selection of traits sharing some common genetic origins with the selected trait. Overall, the major emphasis of my dissertation was two-fold: (1) the elucidation of behavioral traits co-selected with low and high physical activity motivational behavior and (2) the effect of voluntary running in a mildly stressful environment on the dentate gyrus transcriptome of rats selectively bred for low voluntary running. Emphasis 1 (Chapters 2 and 3) was approached by measuring the performance of LVR and HVR rats in behavioral tests classically designed to measure non-wheel running locomotor activity behavior (i.e. open field test), sensitivity to drugs of abuse (i.e. cocaine-induced locomotor activity), anxiety-like behavior (i.e. elevated plus maze), depressive-like behavior (i.e. forced swim test), and nociception (i.e. thermal and mechanical stimulus). Emphasis 2 was approached by using RNA sequencing (RNA-seq) to map the transcriptome of the dentate gyrus after exposing sedentary and wheel running LVR and WT rats to 5 weeks of chronic mild stress (CMS). The results from Chapters 2 and 3 demonstrate that LVR and HVR rats have co-selected other behaviors, which suggest that they may be a valuable model for an array of research disciplines including: (1) the investigation of the genetic basis for physical activity motivation, (2) hyperactivity, (3) sensitivity to drugs of abuse (e.g. addiction), (4) emotional/stress disorders (e.g. anxiety and depression), and (5) nociception as well as the interactions between these complex phenotypes. The results from Chapter 4 provide transcriptomic evidence that low amounts of voluntary running performed by female LVR rats in a CMS environment are sufficient for eliciting robust changes in dentate gyrus transcriptome that included gene expression signatures associated with elevated synaptic plasticity, improved memory function, and increased blood vessel development.

The molecules that move us : evaluating potential genetic and molecular determinants of physical activity motivation

2019 ◽  
Author(s):  
◽  
Kolter Grigsby
Keyword(s):  
Physical Activity ◽  
Kinase Inhibitor ◽  
Wheel Running ◽  
Running Activity ◽  
Voluntary Running ◽  
Molecular Determinants ◽  
Mrna And Protein Expression ◽  
Physical Activity Motivation ◽  
Dopaminergic Pathways

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] Physical activity is at the basis of human history. The fact that we occupy every continent, were built for long distance travel, and that we find reward and value in physical activity, speaks to the notion that we were not designed to be sedentary. That said, physical inactivity remains a major contributor to at least 40 non-communicable diseases, of which heart disease, type-2 diabetes, depression, anxiety, and dementia remain untamed and at the forefront of our public health interests. For the first time in human history, engaging in physical activity is essentially voluntary, a choice that [about] 97% of U.S. adults fail to meet in terms of the U.S. Physical Activity Guidelines. In light of the inactivity epidemic, it follows that finding therapeutics and approaches aimed at reversing or preventing sedentary lifestyles will undoubtedly benefit our global health and well-being. In an attempt to address this possibility, the collective work of this dissertation is made up of three independent studies incorporating wheel-running behavior in a selectively bred rat model of low voluntary running (LVR) behavior. Moreover, these studies address the hypothesis that distinct differences in motivationally-relevant mechanisms within the mesolimbic reward system, in particular the nucleus accumbens (NAc), accompany LVR behavior. In the first study, rats selectively bred for high voluntary running (HVR) or LVR behavior were used to assess inherent differences in both NAc N-methyl-D-aspartate (NMDA) mRNA and protein expression, as well as differences in NMDA-evoked current responses and dopamine release. The data indicate that there were significantly higher levels of mRNA and protein expression of NR1, indicative of higher total NMDA receptor numbers, in HVR compared to LVR rats. There was similarly a greater current response to NMDA in isolated NAc neurons and greater NMDA-evoked dopamine release in NAc tissue from HVR compared to LVR rats. Collectively, these data suggest a likely link between NAc NR1 subunit expression and NMDA function and the predisposition for nightly voluntary running behavior. In study 2, the small kinase inhibitor, Protein Kinase Inhibitor Alpha (PKI[alpha]), was assessed as a potential gene candidate involved in physical activity motivation. Previous work in our lab identified PKl[alpha] as being expressed at low levels in the NAc of LVR compared to HVR rats, with PKl[alpha] expression being positively correlated with running behavior. Due to its key role in dopamine receptor 1 signaling, PKl[alpha] offered a potential target for modulating physical activity motivation. The extent to which PKl[alpha] influences wheel-running behavior and motivation was assessed through site-directed, intra-NAc AAV-mediated overexpression of PKl[alpha]. Following PKl[alpha]overexpression, LVR rats display [about]3-fold higher total running activity over 20 days compared to controls, with no effect of PKl[alpha] overexpression in WT rats. Beyond what appears to be a behavioral resistance in WT rats, there was a noticeably lower dopaminergic transcript expression with PKl[alpha] overexpression in WT rats compared to WT rats expressing the empty-vector control, with no effect seen in LVR rats on dopaminergic expression. From these data, PKl[alpha] appears to be a novel and effective molecular target for reversing low physical activity motivation. To expand knowledge on the critical role of PKl[alpha] in the regulation of dopaminergic signaling, attention shifted to the major downstream transcription factor, CREB. Thus, study 3 addressed the role of NAc CREB in gating voluntary wheel-running motivation, in LVR rats. Results indicate that baseline CREB phosphorylation levels were higher in LVR compared WT rats, suggesting that CREB activation might induce reward and motivational deficits. Further, inducible upstream CREB attenuation via G[i]-coupled hM4Di DREADD or pharmacological inhibition of NAc CREB increased running behavior in LVR but not WT rats. Similarly, environmentally enriched LVR rats exhibit higher running activity compared to socially isolated rats in a CREB-related fashion. To evaluate the role of NAc glutamatergic and dopaminergic pathways in motivational activity, potential genetic and molecular determinants of physical activity motivation were examined. Collectively, findings from these studies suggest that the glutamatergic and dopaminergic pathways play a role in physical activity motivation in the LVR rats, which encourages future efforts to target these pathways to enhance physical activity in humans.

Methamphetamine-induced hyperactivity and reinforcement learning in rats selectively bred for high and low voluntary running

2015 ◽  
Author(s):  
◽  
Andrew S. Sage
Keyword(s):  
Wheel Running ◽  
Food Pellet ◽  
Preliminary Investigation ◽  
Voluntary Exercise ◽  
University Of Missouri ◽  
Voluntary Running ◽  
Lever Pressing ◽  
Necessary And Sufficient ◽  
The University

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] The goal of the present research was to assess two lines of Wistar rats selectively bred for high (HVR) and low (LVR) voluntary wheel running, in comparison to a line of control (WT) rats. As previous research has outlined the benefits of voluntary exercise on substance abuse, this study investigated the role of possible genetic differences between rat lines on sensitivity to methamphetamine (Experiment 1), motivation to work for and self-administer methamphetamine (Experiment 2a), and learning to press a lever for a food reward (Experiment 2b). Experiment 1 investigated sensitivity to methamphetamine in HVR, LVR, and WT rats by comparing locomotor behavior after methamphetamine administration. Experiment 1 found that both HVR and LVR rats were less sensitive to the locomotor activating properties of methamphetamine compared to WT rats. Experiment 2a and 2b investigated learning to press a lever for a food pellet or an infusion of methamphetamine in HVR, LVR, and WT rats. Experiment 2a found that both HVR and LVR rats were less sensitive to the reinforcing properties of methamphetamine compared to WT rats, evidenced by their reduced lever pressing behavior. Experiment 2b found that HVR rats pressed a lever less for a food pellet compared to both LVR and WT rats, suggesting that HVR rats alone may value a food pellet as a behavioral reinforcer less than the other two rat lines. The results of this preliminary investigation suggest that exercise may be both necessary and sufficient to produce effects on drug use behaviors. One's (genetic) predisposition to engage in exercise may be independent of one's ability to benefit from exercise.

Examination of biological factors that mediate the influence of physical activity on palatability driven feeding

2019 ◽  
Author(s):  
◽  
Jenna R. Lee
Keyword(s):  
Physical Activity ◽  
Physiological Response ◽  
Neural Mechanisms ◽  
Target System ◽  
Biological Factors ◽  
University Of Missouri ◽  
Male And Female ◽  
Behavioral Adaptations ◽  
Voluntary Physical Activity ◽  
The University

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] Palatability driven feeding- consuming food for pleasure, and voluntary physical activity are mediated by and influence similar neural mechanisms. However, the interaction between the two behaviors is not well established. Considering both behaviors are facilitated by opioids within the nucleus accumbens (NAc), it is a likely target system to arbitrate such effects. Furthermore, it is yet to be determined how biological factors between subjects such as sex or genetics may influence this interaction. The experiments presented in this dissertation utilize unique models applying systems and behavioral neuroscience approaches to test the hypothesis that differences in biological factors may mediate the effect of physical activity on palatability driven feeding. All studies included both male and female subjects in order to account for potential sex differences in the behavioral and physiological response to physical activity. These studies suggest that males may decrease consumption of palatable diets in response to physical activity through a potential opioid related habituation mechanism. Conversely, females may undergo an alterative response to physical activity, resulting in an increased consumption of palatable diets. This may occur through a potential opioid related sensitization mechanism. The second study included selectively bred rats to further explore biological factors related to motivation that may arbitrate the physiological and behavioral adaptations in response to physical activity.

scholarly journals Synaptic Remodeling in the Dentate Gyrus, CA3, CA1, Subiculum, and Entorhinal Cortex of Mice: Effects of Deprived Rearing and Voluntary Running

2010 ◽  
Vol 2010 ◽  
pp. 1-11 ◽  
Author(s):  
Andrea T. U. Schaefers ◽  
Keren Grafen ◽  
Gertraud Teuchert-Noodt ◽  
York Winter
Keyword(s):  
Dentate Gyrus ◽  
Entorhinal Cortex ◽  
Neural Plasticity ◽  
Wheel Running ◽  
Meriones Unguiculatus ◽  
Turnover Rates ◽  
Synaptic Remodeling ◽  
Epigenetic Effect ◽  
Voluntary Running ◽  
Juvenile Development

Hippocampal cell proliferation is strongly increased and synaptic turnover decreased after rearing under social and physical deprivation in gerbils (Meriones unguiculatus). We examined if a similar epigenetic effect of rearing environment on adult neuroplastic responses can be found in mice (Mus musculus). We examined synaptic turnover rates in the dentate gyrus, CA3, CA1, subiculum, and entorhinal cortex. No direct effects of deprived rearing on rates of synaptic turnover were found in any of the studied regions. However, adult wheel running had the effect of leveling layer-specific differences in synaptic remodeling in the dentate gyrus, CA3, and CA1, but not in the entorhinal cortex and subiculum of animals of both rearing treatments. Epigenetic effects during juvenile development affected adult neural plasticity in mice, but seemed to be less pronounced than in gerbils.

Plastic and evolved morphological responses of the hind limb skeleton to mechanical loading in mice

2018 ◽  
Author(s):  
◽  
Amanda Smolinsky
Keyword(s):  
Phenotypic Plasticity ◽  
Mechanical Loading ◽  
Hind Limb ◽  
Cross Sectional ◽  
Skeletal Morphology ◽  
University Of Missouri ◽  
Voluntary Running ◽  
Mechanisms Of Adaptation ◽  
The University ◽  
Insight Into

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Skeletal morphology is determined by a combination of genetic background and phenotypic plasticity induced by mechanical loading. The changes in limb bone morphology associated with locomotor activity through ontogeny and over evolutionary time can provide insight into the mechanisms of adaptation in locomotor systems. Here, a mouse model is used to explore the effects of mechanical loading and locomotor selection on skeletal morphology and phenotypic plasticity. The source of loading (muscular, ground reaction, or combined forces) was found to differentially affect the pattern and rate of mineral apposition at the mid-diaphysis of the femur, and the femoral cross-sectional morphology produced by running locomotion appears to be most influenced by muscular forces. Loading environment also differentially altered the gross shapes of the hind limb bones, and a blending of the influence of ground reaction and muscular forces was observed in the bones of running mice. Finally, artificial selection for increased voluntary running distance resulted in evolved changes in skeletal morphology and the plastic response of bone to mechanical loading. The results suggest regional sensitivity of skeleton to morphological change and inform our understanding of the plastic and evolutionary lability of the skeleton.

TEM study of boron additions to cobalt aluminide

1988 ◽  
Vol 46 ◽  
pp. 546-547
Author(s):  
Gerald B. Feldewerth
Keyword(s):  
High Temperature ◽  
Turbine Engines ◽  
Major Drawback ◽  
University Of Missouri ◽  
Specific Strength ◽  
Aerospace Applications ◽  
Wide Range ◽  
Ordered Alloys ◽  
The University ◽  
Very High

In recent years an increasing emphasis has been placed on the study of high temperature intermetallic compounds for possible aerospace applications. One group of interest is the B2 aiuminides. This group of intermetaliics has a very high melting temperature, good high temperature, and excellent specific strength. These qualities make it a candidate for applications such as turbine engines. The B2 aiuminides exist over a wide range of compositions and also have a large solubility for third element substitutional additions, which may allow alloying additions to overcome their major drawback, their brittle nature.One B2 aluminide currently being studied is cobalt aluminide. Optical microscopy of CoAl alloys produced at the University of Missouri-Rolla showed a dramatic decrease in the grain size which affects the yield strength and flow stress of long range ordered alloys, and a change in the grain shape with the addition of 0.5 % boron.

MARS — Its Tenth Anniversary of Operation and its Future

1980 ◽  
Vol 19 (03) ◽  
pp. 125-132
Author(s):  
G. S. Lodwick ◽  
C. R. Wickizer ◽  
E. Dickhaus
Keyword(s):  
Conceptual Development ◽  
Administrative Support ◽  
Final Section ◽  
Economic Benefits ◽  
Hospital Environment ◽  
Computer Scientist ◽  
University Of Missouri ◽  
Complete Bibliography ◽  
The University ◽  
Economic Considerations

The Missouri Automated Radiology System recently passed its tenth year of clinical operation at the University of Missouri. This article presents the views of a radiologist who has been instrumental in the conceptual development and administrative support of MARS for most of this period, an economist who evaluated MARS from 1972 to 1974 as part of her doctoral dissertation, and a computer scientist who has worked for two years in the development of a Standard MUMPS version of MARS. The first section provides a historical perspective. The second deals with economic considerations of the present MARS system, and suggests those improvements which offer the greatest economic benefits. The final section discusses the new approaches employed in the latest version of MARS, as well as areas for further application in the overall radiology and hospital environment. A complete bibliography on MARS is provided for further reading.

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