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.

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 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 Insight into Salivary Gland Aquaporins

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1547 ◽  
Author(s):  
Claudia D’Agostino ◽  
Osama A. Elkashty ◽  
Clara Chivasso ◽  
Jason Perret ◽  
Simon D. Tran ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Physiological Role ◽  
Main Role ◽  
Osmotic Gradient ◽  
Therapeutic Approaches ◽  
Potential Therapeutic Target ◽  
Transmembrane Channel ◽  
Saliva Secretion ◽  
Insight Into

The main role of salivary glands (SG) is the production and secretion of saliva, in which aquaporins (AQPs) play a key role by ensuring water flow. The AQPs are transmembrane channel proteins permeable to water to allow water transport across cell membranes according to osmotic gradient. This review gives an insight into SG AQPs. Indeed, it gives a summary of the expression and localization of AQPs in adult human, rat and mouse SG, as well as of their physiological role in SG function. Furthermore, the review provides a comprehensive view of the involvement of AQPs in pathological conditions affecting SG, including Sjögren’s syndrome, diabetes, agedness, head and neck cancer radiotherapy and SG cancer. These conditions are characterized by salivary hypofunction resulting in xerostomia. A specific focus is given on current and future therapeutic strategies aiming at AQPs to treat xerostomia. A deeper understanding of the AQPs involvement in molecular mechanisms of saliva secretion and diseases offered new avenues for therapeutic approaches, including drugs, gene therapy and tissue engineering. As such, AQP5 represents a potential therapeutic target in different strategies for the treatment of xerostomia.

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

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

2016 ◽  
Vol 48 (2) ◽  
pp. 101-115 ◽  
Author(s):  
Ryan G. Toedebusch ◽  
Gregory N. Ruegsegger ◽  
Joshua F. Braselton ◽  
Alexander J. Heese ◽  
John C. Hofheins ◽  
...  
Keyword(s):  
Protein Concentration ◽  
Molecular Mechanisms ◽  
Outcome Measure ◽  
Wheel Running ◽  
Female Rats ◽  
Peak Oxygen Consumption ◽  
Chronological Age ◽  
Primary Hypothesis ◽  
Running Wheels ◽  
Voluntary Wheel

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 (0.5 mg/g/day) subcutaneously for 5 wk beginning at 17 wk of age. All rats underwent frequent, weekly or biweekly V̇o2 peak tests beginning at 10 wk of age. In experiment 1, lifetime-apex V̇o2 peak occurred at 19 wk of age in both RUN and NO RUN and decreased thereafter. V̇o2 peak measured across experiment 1 was ∼25% higher in RUN than in NO RUN. In experiment 2, AICAR delayed the chronological age observed in experiment 1 by 1 wk, from 19 wk to 20 wk of age. RUN and NO RUN showed different skeletal muscle transcriptomic profiles both pre- and postapex. Additionally, growth and development pathways are differentially regulated between RUN and NO RUN. Angiomotin mRNA was downregulated postapex in RUN and NO RUN. Furthermore, strong significant correlations to V̇o2 peak and trends for decreased protein concentration supports angiomotin's potential importance in our model. Contrary to our primary hypothesis, wheel running was not sufficient to delay the chronological age of lifetime-apex V̇o2 peak decline, whereas AICAR delayed it 1 wk.

scholarly journals Label-Free Proteomic Analysis of Smoke-Drying and Shade-Drying Processes of Postharvest Rhubarb: A Comparative Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Wei Liang ◽  
Yuan Chen ◽  
Xia Li ◽  
Fengxia Guo ◽  
Jiachen Sun ◽  
...  
Keyword(s):  
Molecular Mechanism ◽  
Molecular Mechanisms ◽  
Drying Methods ◽  
Label Free ◽  
Pharmacological Activities ◽  
Dry Process ◽  
Insight Into ◽  
Differentially Abundant Proteins ◽  
Postharvest Processing

Postharvest processing plays a very important role in improving the quality of traditional Chinese medicine. According to previous studies, smoke-drying could significantly promote the accumulation of the bioactive components and pharmacological activities of rhubarb, but so far, the molecular mechanism has not been studied yet. In this research, to study the molecular mechanisms of postharvest processing for rhubarb during shade-drying and smoke-drying, label-free proteomic analyses were conducted. In total, 1,927 differentially abundant proteins (DAPs) were identified from rhubarb samples treated by different drying methods. These DAPs were mainly involved in response and defense, signal transduction, starch, carbohydrate and energy metabolism, and anthraquinone and phenolic acid biosynthesis. Smoke-drying significantly enhanced the expression of proteins involved in these metabolic pathways. Accordingly, the molecular mechanism of the accumulation of effective ingredients of rhubarb was clarified, which provided a novel insight into the biosynthesis of active ingredients that occur during the rhubarb dry process.

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.

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