scholarly journals Examination of nucleus accumbens mechanisms underlying the motivation for physical activity

2017 ◽  
Author(s):  
◽  
Gregory Neal Ruegsegger
Keyword(s):  
Physical Activity ◽  
Nucleus Accumbens ◽  
Molecular Mechanisms ◽  
Leptin Receptor ◽  
Wheel Running ◽  
Receptor Expression ◽  
Voluntary Wheel Running ◽  
Age Related ◽  
Voluntary Physical Activity ◽  
Voluntary Wheel

Physical inactivity, a primary contributor to numerous diseases including obesity, type 2 diabetes, depression, and dementia, has reached pandemic levels worldwide. Alarmingly, the percentage of individuals engaging in physical activity is low and decreasing. Accelerometry data shows that > 90% of adults fail to meet the U.S. Physical Activity Guidelines despite the excess of knowledge suggesting exercise improves health. Therefore, beginning to understand the molecular mechanisms which influence physical activity levels is imperative for the development of therapies to reduce sedentary behavior. The work presented in this dissertation made use of three independent experimental paradigms in rats to test the hypothesis that differences in the mesolimbic dopamine system associate with/cause changes in voluntary physical activity. In the first study, rats selectively bred for high (HVR) or low (LVR) voluntary wheel running distance were used to assess inherent differences in opioidergic signaling between HVR and LVR, as well as the influence of dopamine on opioid-induced changes in voluntary wheel running. Mu-opioid receptor expression and function was increased in the nucleus accumbens (NAc) of HVR compared to LVR. Likewise, naltrexone injection decreased dopamine-related mRNA expression in mesolimbic brain regions and reduced wheel running in HVR, but not LVR. Finally, lesion of dopaminergic neurons in the NAc prevented the decrease in running following naltrexone administration in HVR, suggesting opioidergic signaling requires downstream dopaminergic activity to influence voluntary running. In the second study, the transgenerational effect of maternal Western diet (WD) on offspring voluntary wheel running was assessed. Wheel running was increased in female WD offspring from 4-7 weeks of age, but decreased running from 16-19 weeks of age, compared to offspring from chow fed dams. These age-specific changes in wheel running are associated with the up- and down-regulation of dopamine receptor 1 in the NAc at 6 and 18 weeks of age, respectively, in WD female offspring, which in turn was negatively associated with leptin receptor mRNA in the ventral tegmental area. In the third study, age-related influences on wheel running were assessed in 8 and 14 week-old rats. In addition to a [about]60% reduction in running, RNA-sequencing revealed down-regulations in networks related to cAMP-mediated signaling and synaptic plasticity in the NAc from 8 to 14 weeks-old. The down-regulations of these networks was mirrored by reductions in dendritic spine density in the NAc from 8 to 14 weeks-old. Additionally, intra-NAc injection of the Cdk5 inhibitor roscovitine, a known modulator of dendritic density and dopamine signaling, dose-dependently decreased wheel running. Despite the varying experimental models used in this dissertation, these findings collectively suggest that alterations in dopaminergic signaling in the NAc associate with, and influence, voluntary physical activity.

Voluntary wheel running ameliorates vascular smooth muscle hyper-contractility in type 2 diabetic db/db mice

2007 ◽  
Vol 32 (4) ◽  
pp. 711-720 ◽  
Author(s):  
Karyn A. Esser ◽  
Wen Su ◽  
Sergey Matveev ◽  
Vicki Wong ◽  
Li Zeng ◽  
...  
Keyword(s):  
Physical Activity ◽  
Smooth Muscle ◽  
Blood Glucose ◽  
Vascular Smooth Muscle ◽  
Wheel Running ◽  
Voluntary Wheel Running ◽  
Voluntary Physical Activity ◽  
Type 2 Diabetic ◽  
Voluntary Wheel

Physical activity reduces cardiovascular disease related mortality in diabetic patients. However, it is unknown if the diabetic state reduces voluntary physical activity and, if so, if the voluntary physical activity at the reduced level is sufficient to improve cardiovascular risk factors. To address these two specific questions, we investigated voluntary wheel running performance in an obese and type 2 diabetic mouse model, the db/db mice. In addition, we determined the effects of running on body mass, blood glucose, insulin, plasma free fatty acids, cholesterol, and vascular smooth muscle hyper-contractility. Our results showed that daily running distance, time, and speed were significantly reduced in the db/db mice to about 23%, 32%, and 71%, respectively, of that in non-diabetic control mice. However, this low level of running was sufficient to induce a reduction in the vascular smooth muscle hyper-contractility, cholesterol, and some plasma free fatty acids, as well as to delay the decrease in blood insulin. These changes occurred in the absence of weight loss and a detectable decrease in blood glucose. Thus, the results of this study demonstrated that voluntary wheel running activity was dramatically reduced in db/db mice. However, the low levels of running were beneficial, in the absence of effects on obesity or blood glucose, with significant reductions in cardiovascular risk factors and potential delays in β-cell dysfunction.

scholarly journals Interrelationship of CB1R and OBR pathways in regulation of metabolic, neuroendocrine, and behavioral responses to food restriction and voluntary wheel running

2014 ◽  
Vol 117 (2) ◽  
pp. 97-104 ◽  
Author(s):  
Abdoulaye Diane ◽  
Donna F. Vine ◽  
James C. Russell ◽  
C. Donald Heth ◽  
W. David Pierce ◽  
...  
Keyword(s):  
Physical Activity ◽  
Body Weight ◽  
Food Restriction ◽  
Leptin Receptor ◽  
Wheel Running ◽  
Behavioral Responses ◽  
Voluntary Wheel Running ◽  
Cannabinoid 1 Receptor ◽  
Clinical Measures ◽  
Voluntary Wheel

We hypothesized the cannabinoid-1 receptor and leptin receptor (ObR) operate synergistically to modulate metabolic, neuroendocrine, and behavioral responses of animals exposed to a survival challenge (food restriction and wheel running). Obese-prone (OP) JCR:LA- cp rats, lacking functional ObR, and lean-prone (LP) JCR:LA- cp rats (intact ObR) were assigned to OP-C and LP-C (control) or CBR1-antagonized (SR141716, 10 mg/kg body wt in food) OP-A and LP-A groups. After 32 days, all rats were exposed to 1.5-h daily meals without the drug and 22.5-h voluntary wheel running, a survival challenge that normally culminates in activity-based anorexia (ABA). Rats were removed from the ABA protocol when body weight reached 75% of entry weight (starvation criterion) or after 14 days (survival criterion). LP-A rats starved faster (6.44 ± 0.24 days) than LP-C animals (8.00 ± 0.29 days); all OP rats survived the ABA challenge. LP-A rats lost weight faster than animals in all other groups ( P < 0.001). Consistent with the starvation results, LP-A rats increased the rate of wheel running more rapidly than LP-C rats ( P = 0.001), with no difference in hypothalamic and primary neural reward serotonin levels. In contrast, OP-A rats showed suppression of wheel running compared with the OP-C group ( days 6–14 of ABA challenge, P < 0.001) and decreased hypothalamic and neural reward serotonin levels ( P < 0.01). Thus there is an interrelationship between cannabinoid-1 receptor and ObR pathways in regulation of energy balance and physical activity. Effective clinical measures to prevent and treat a variety of disorders will require understanding of the mechanisms underlying these effects.

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

2016 ◽  
Vol 595 (1) ◽  
pp. 363-384 ◽  
Author(s):  
Gregory N. Ruegsegger ◽  
Ryan G. Toedebusch ◽  
Thomas E. Childs ◽  
Kolter B. Grigsby ◽  
Frank W. Booth
Keyword(s):  
Physical Activity ◽  
Nucleus Accumbens ◽  
Wheel Running ◽  
Age Related ◽  
Voluntary Physical Activity

scholarly journals Chronic environmental or genetic elevation of galanin in noradrenergic neurons confers stress resilience in mice

2020 ◽  
Author(s):  
Rachel P. Tillage ◽  
Genevieve E. Wilson ◽  
L. Cameron Liles ◽  
Philip V. Holmes ◽  
David Weinshenker
Keyword(s):  
Physical Activity ◽  
Locus Coeruleus ◽  
Wheel Running ◽  
Neuropsychiatric Disorders ◽  
Noradrenergic Neurons ◽  
Stress Resilience ◽  
Voluntary Wheel Running ◽  
Exercise Induced ◽  
Species Specific ◽  
Voluntary Wheel

ABSTRACTThe neuropeptide galanin has been implicated in stress-related neuropsychiatric disorders in both humans and rodent models. While pharmacological treatments for these disorders are ineffective for many individuals, physical activity is beneficial for stress-related symptoms. Galanin is highly expressed in the noradrenergic system, particularly the locus coeruleus (LC), which is dysregulated in stress-related disorders and activated by exercise. Galanin expression is elevated in the LC by chronic exercise, and blockade of galanin transmission attenuates exercise-induced stress resilience. However, most research on this topic has been done in rats, so it is unclear whether the relationship between exercise and galanin is species-specific. Moreover, use of intracerebroventricular galanin receptor antagonists in prior studies precluded defining a causal role for LC-derived galanin specifically. Therefore, the goals of this study were twofold. First, we investigated whether physical activity (chronic voluntary wheel running) increases stress resilience and galanin expression in the LC of mice. Next, we used transgenic mice that overexpress galanin in noradrenergic neurons (Gal OX) to determine how chronically elevated noradrenergic-derived galanin, alone, alters anxiogenic-like responses to stress. We found that three weeks of ad libitum access to a running wheel in their home cage increased galanin mRNA in the LC of mice and conferred resilience to a stressor. The effects of exercise were phenocopied by galanin overexpression in noradrenergic neurons, and Gal OX mice were resistant to the anxiogenic effect of optogenetic LC activation. Together, these findings support a role for chronically increased noradrenergic galanin in mediating resilience to stress.Significance statementUnderstanding the neurobiological mechanisms underlying behavioral responses to stress is necessary to improve treatments for stress-related neuropsychiatric disorders. Increased physical activity is associated with stress resilience in humans, but the neurobiological mechanisms underlying this effect are not clear. Here we investigate the anxiolytic potential of the neuropeptide galanin from the main noradrenergic nucleus, the locus coeruleus (LC). We show that chronic voluntary wheel running in mice galanin expression in the LC and stress resilience. Furthermore, we show that genetic overexpression of galanin in noradrenergic neurons confers resilience to the anxiogenic effects of foot shock and optogenetic LC activation. These findings support a role for chronically increased noradrenergic galanin in mediating resilience to stress.

scholarly journals Voluntary exercise and depression-like behavior in rodents: are we running in the right direction?

2018 ◽  
Vol 60 (3) ◽  
pp. R77-R95 ◽  
Author(s):  
Joram D Mul
Keyword(s):  
Exercise Training ◽  
Molecular Mechanisms ◽  
Wheel Running ◽  
Financial Burden ◽  
Modern Society ◽  
Mental Illnesses ◽  
Voluntary Exercise ◽  
Voluntary Wheel Running ◽  
Beneficial Effects ◽  
Voluntary Wheel

Acute or chronic exposure to stress can increase the risk to develop major depressive disorder, a severe, recurrent and common psychiatric condition. Depression places an enormous social and financial burden on modern society. Although many depressed patients are treated with antidepressants, their efficacy is only modest, underscoring the necessity to develop clinically effective pharmaceutical or behavioral treatments. Exercise training produces beneficial effects on stress-related mental disorders, indicative of clinical potential. The pro-resilient and antidepressant effects of exercise training have been documented for several decades. Nonetheless, the underlying molecular mechanisms and the brain circuitries involved remain poorly understood. Preclinical investigations using voluntary wheel running, a frequently used rodent model that mimics aspects of human exercise training, have started to shed light on the molecular adaptations, signaling pathways and brain nuclei underlying the beneficial effects of exercise training on stress-related behavior. In this review, I highlight several neurotransmitter systems that are putative mediators of the beneficial effects of exercise training on mental health, and review recent rodent studies that utilized voluntary wheel running to promote our understanding of exercise training-induced central adaptations. Advancements in our mechanistic understanding of how exercise training induces beneficial neuronal adaptations will provide a framework for the development of new strategies to treat stress-associated mental illnesses.

scholarly journals Physical Activity Dynamically Regulates the Hippocampal Proteome along the Dorso-Ventral Axis

2020 ◽  
Vol 21 (10) ◽  
pp. 3501
Author(s):  
Surina Frey ◽  
Rico Schieweck ◽  
Ignasi Forné ◽  
Axel Imhof ◽  
Tobias Straub ◽  
...  
Keyword(s):  
Physical Activity ◽  
Regional Differences ◽  
Molecular Mechanisms ◽  
Wheel Running ◽  
Actin Binding ◽  
Label Free ◽  
Therapeutic Approaches ◽  
Cytoskeleton Remodeling ◽  
Insight Into ◽  
Voluntary Wheel

The hippocampus is central for higher cognition and emotions. In patients suffering from neuropsychiatric or neurodegenerative diseases, hippocampal signaling is altered causing cognitive defects. Thus, therapeutic approaches aim at improving cognition by targeting the hippocampus. Enhanced physical activity (EPA) improves cognition in rodents and humans. A systematic screen, however, for expression changes in the hippocampus along the dorso-ventral axis is missing, which is a prerequisite for understanding molecular mechanisms. Here, we exploited label free mass spectrometry to detect proteomic changes in the hippocampus of male mice upon voluntary wheel running. To identify regional differences, we examined dorsal and ventral CA1, CA3 and dentate gyrus hippocampal subregions. We found metabolic enzymes and actin binding proteins, such as RhoA, being upregulated in the hippocampus upon EPA suggesting a coordination between metabolism and cytoskeleton remodeling; two pathways essential for synaptic plasticity. Strikingly, dorsal and ventral hippocampal subregions respond differentially to EPA. Together, our results provide new insight into proteomic adaptations driven by physical activity in mice. In addition, our results suggest that dorsal and ventral hippocampus, as well as hippocampal subregions themselves, contribute differently to this process. Our study therefore provides an important resource for studying hippocampal subregion diversity in response to EPA.

Sex dependent effects of physical activity on diet preference in rats selectively bred for high or low levels of voluntary wheel running

2019 ◽  
Vol 359 ◽  
pp. 95-103 ◽  
Author(s):  
Jenna R. Lee ◽  
Melissa A. Tapia ◽  
Jane R. Nelson ◽  
Justin M. Moore ◽  
Graydon B. Gereau ◽  
...  
Keyword(s):  
Physical Activity ◽  
Wheel Running ◽  
Voluntary Wheel Running ◽  
Diet Preference ◽  
Low Levels ◽  
Voluntary Wheel
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