scholarly journals Hippocampal Morphology in a Rat Model of Depression: The Effects of Physical Activity

2015 ◽  
Vol 9 (1) ◽  
pp. 1-6 ◽  
Author(s):  
Adam Sierakowiak ◽  
Anna Mattsson ◽  
Marta Gómez-Galán ◽  
Teresa Feminía ◽  
Lisette Graae ◽  
...  

Accumulating in vivo and ex vivo evidences show that humans suffering from depression have decreased hippocampal volume and altered spine density. Moreover, physical activity has an antidepressant effect in humans and in animal models, but to what extent physical activity can affect hippocampal volume and spine numbers in a model for depression is not known. In this study we analyzed whether physical activity affects hippocampal volume and spine density by analyzing a rodent genetic model of depression, Flinders Sensitive Line Rats (FSL), with Magnetic Resonance Imaging (MRI) and ex vivo Golgi staining. We found that physical activity in the form of voluntary wheel running during 5 weeks increased hippocampal volume. Moreover, runners also had larger numbers of thin spines in the dentate gyrus. Our findings support that voluntary wheel running, which is antidepressive in FSL rats, is associated with increased hippocampal volume and spine numbers.

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Suowen Xu ◽  
Marina Koroleva ◽  
Keigi Fujiwara ◽  
Zheng Gen Jin

Introduction: Impaired activation of endothelial nitric oxide (NO) synthase (eNOS) and ensued NO production is a common mechanism of various cardiovascular pathologies, including hypertension and atherosclerosis. Specific signaling cascades, generated by vascular endothelial cells (ECs) in response to laminar flow, modulate EC structure and functions, NO production in particular. We have previously shown that flow-stimulated Gab1 (Grb2-associated binder-1) tyrosine phosphorylation mediates eNOS activation. However, the upstream mechanism that regulates Gab1 tyrosine phosphorylation remains unclear. Hypothesis: We hypothesized that platelet endothelial cell adhesion molecule-1 (PECAM1), a key molecule in an endothelial mechanosensing complex, specifically mediates Gab1 tyrosine phosphorylation and its downstream Akt and eNOS activation in ECs upon flow rather than hepatocyte growth factor (HGF) stimulation. Methods: Western blot, en face staining and voluntary wheel running. Results: Small interfering RNA (siRNA) targeting PECAM1 abolished flow- but not HGF-induced Gab1 tyrosine phosphorylation and Akt, eNOS activation as well as Gab1 membrane translocation. Protein-tyrosine phosphatase SHP2, which has been shown to interact with Gab1, was involved in a flow signaling pathway as well as HGF-induced signaling, as SHP2 siRNA diminished the flow- and HGF-induced Gab1 tyrosine phosphorylation, membrane localization and downstream signaling. Pharmacological inhibition of PI3K by LY294002 decreased flow, but not HGF-mediated Gab1 phosphorylation and membrane localization as well as eNOS activation. Finally, we observed that flow-mediated Gab1 and eNOS phosphorylation in vivo induced by voluntary wheel running was reduced in PECAM1 knockout mice. Conclusions: These results demonstrate a specific role of PECAM1 in flow-mediated Gab1 tyrosine phosphorylation and eNOS signaling in ECs


1999 ◽  
Vol 86 (4) ◽  
pp. 1374-1380 ◽  
Author(s):  
Deborah A. Podolin ◽  
Yuren Wei ◽  
Michael J. Pagliassotti

The purpose of the present study was to determine the effects of diet composition and exercise on glycerol and glucose appearance rate (Ra) and on nonglycerol gluconeogenesis (Gneo) in vivo. Male Wistar rats were fed a high-starch diet (St, 68% of energy as cornstarch, 12% corn oil) for a 2-wk baseline period and then were randomly assigned to one of four experimental groups: St ( n = 7), high-fat (HF; 35% cornstarch, 45% corn oil; n = 8), St with free access to exercise wheels (StEx; n = 7), and HF with free access to exercise wheels (HFEx; n = 7). After 8 wk, glucose Rawhen using [3-3H]glucose, glycerol Rawhen using [2H5]glycerol (estimate of whole body lipolysis), and [3-13C]alanine incorporation into glucose (estimate of alanine Gneo) were determined. Body weight and fat pad mass were significantly ( P < 0.05) decreased in exercise vs. sedentary animals only. The average amount of exercise was not significantly different between StEx (3,212 ± 659 m/day) and HFEx (3,581 ± 765 m/day). The ratio of glucose to alanine enrichment and absolute glycerol Ra(μmol/min) were higher ( P < 0.05) in HF and HFEx compared with St and StEx rats. In separate experiments, the ratio of3H in C-2 to C-6 of glucose from3H2O (estimate of Gneo from pyruvate) was also higher ( P < 0.05) in HF ( n = 5) and HFEx ( n = 5), compared with St ( n = 5) and StEx ( n = 5) rats. Voluntary wheel running did not significantly increase estimated alanine or pyruvate Gneo or absolute glycerol Ra. Voluntary wheel running increased ( P< 0.05) glycerol Rawhen normalized to fat pad mass. These data suggest that a high-fat diet can increase in vivo Gneo from precursors that pass through pyruvate. They also suggest that changes in the absolute rate of glycerol Ramay contribute to the high-fat diet-induced increase in Gneo.


2007 ◽  
Vol 32 (4) ◽  
pp. 711-720 ◽  
Author(s):  
Karyn A. Esser ◽  
Wen Su ◽  
Sergey Matveev ◽  
Vicki Wong ◽  
Li Zeng ◽  
...  

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.


2020 ◽  
Author(s):  
Rachel P. Tillage ◽  
Genevieve E. Wilson ◽  
L. Cameron Liles ◽  
Philip V. Holmes ◽  
David Weinshenker

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.


2019 ◽  
Vol 359 ◽  
pp. 95-103 ◽  
Author(s):  
Jenna R. Lee ◽  
Melissa A. Tapia ◽  
Jane R. Nelson ◽  
Justin M. Moore ◽  
Graydon B. Gereau ◽  
...  

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Linlin Zhang ◽  
Yi Feng ◽  
Wenliang Ji ◽  
Jianzhang Liu ◽  
Kun Liu

The aim of the present study is to evaluate the effect of voluntary wheel running on striatal dopamine level and behavior of cognition and emotion in molar loss rats. Twenty-four Sprague-Dawley rats were enrolled in this study and randomly divided into following 4 groups: control group (C group), molar loss group (ML group), 1-week physical exercise before molar loss group (1W-ML group), and 4-week physical exercise before molar loss group (4W-ML group). The rats both in 4W-ML and 1W-ML groups were placed in the voluntary running wheel in order to exercise for 4 weeks and 1 week, respectively. Then, the rats in 4W-ML, 1W-M, and ML groups received bilateral molar loss operation. After 10 days, striatal dopamine level was detected by in vivo microdialysis coupled with high-performance liquid chromatography (HPLC) and electrochemical detection. All the rats received behavior test after microdialysis detection. The behavior tests including passive avoidance test were used to assess cognition and elevated plus maze test for emotion. The results indicated that voluntary wheel running promoted striatal dopamine level in rats of molar loss. Behavioral data indicated that voluntary wheel running promoted cognition and emotion recovery after molar loss. Therefore, we concluded physical exercise significantly improved the neurocognitive behaviors and increased the striatal dopamine level after molar loss in rats.


2020 ◽  
Author(s):  
Rachel Stones ◽  
Mark Drinkhill ◽  
Ed White

AbstractRegular mild exercise is recommended to the general population as beneficial to health. Regular exercise typically leads to structural and electrical remodelling of the heart but in human studies it is difficult to relate the extrinsic and intrinsic influences on intact hearts to changes seen at the single cell level. In this study we wished to test whether changes in electrical activity in intact hearts, in response to voluntary wheel running exercise training, were consistent with our previous observations in single cardiac myocytes and whether these changes resulted in altered susceptibility to arrhythmic stimuli.Female rats performed 5 weeks of voluntary wheel running. Implanted telemetry transmitters were used to measure electrocardiograms (ECGs) and determine heart rate variability (HRV) in conscious, unrestrained, trained (TRN) and sedentary (SED) animals. In isolated hearts, left ventricular epicardial monophasic action potentials (MAPs) were recorded and the responses to potentially arrhythmic interventions were assessed.Exercise training caused cardiac hypertrophy, as indexed by a significantly greater heart weight to body weight ratio. Consistent with previous measurements of action potential duration in single myocytes, MAPs were significantly longer at 50%, 75% and 90% repolarization. Arrhythmic susceptibility was not different between SED and TRN hearts. Trained animals displayed significantly altered HRV by week 5, in a manner consistent with reduced sympathetic tone, however resting ECG parameters, including those most associated with repolarisation duration, were unaltered. We conclude that intrinsic changes to cellular cardiac electrophysiology, induced by mild voluntary exercise, are not attenuated by the electronic loading that occurs in intact hearts. However, in vivo, extrinsic neuro-hormonal control of the heart may minimize the effects of intrinsic alterations in electrical activity.


2014 ◽  
Vol 117 (2) ◽  
pp. 97-104 ◽  
Author(s):  
Abdoulaye Diane ◽  
Donna F. Vine ◽  
James C. Russell ◽  
C. Donald Heth ◽  
W. David Pierce ◽  
...  

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.


2018 ◽  
Vol 124 (6) ◽  
pp. 1616-1628 ◽  
Author(s):  
Matthew J. Brooks ◽  
Ameena Hajira ◽  
Junaith S. Mohamed ◽  
Stephen E. Alway

Reloading of atrophied muscles after hindlimb suspension unloading (HSU) can induce injury and prolong recovery. Low-impact exercise, such as voluntary wheel running, has been identified as a nondamaging rehabilitation therapy in rodents, but its effects on muscle function, morphology, and satellite cell activity after HSU are unclear. This study tested the hypothesis that low-impact wheel running would increase satellite cell proliferation and improve recovery of muscle structure and function after HSU in mice. Young adult male and female C57BL/6 mice ( n = 6/group) were randomly placed into five groups. These included HSU without recovery (HSU), normal ambulatory recovery for 14 days after HSU (HSU+NoWR), and voluntary wheel running recovery for 14 days after HSU (HSU+WR). Two control groups were used: nonsuspended mouse cage controls (Control) and voluntary wheel running controls (ControlWR). Satellite cell activation was evaluated by providing mice 5-bromo-2′-deoxyuridine (BrdU) in their drinking water. As expected, HSU significantly reduced in vivo maximal force, decreased in vivo fatigability, and decreased type I and IIa myosin heavy chain (MHC) abundance in plantarflexor muscles. HSU+WR mice significantly improved plantarflexor fatigue resistance, increased type I and IIa MHC abundance, increased fiber cross-sectional area, and increased the percentage of type I and IIA muscle fibers in the gastrocnemius muscle. HSU+WR mice also had a significantly greater percentage of BrdU-positive and Pax 7-positive nuclei inside muscle fibers and a greater MyoD-to-Pax 7 protein ratio compared with HSU+NoWR mice. The mechanotransduction protein Yes-associated protein (YAP) was elevated with reloading after HSU, but HSU+WR mice had lower levels of the inactive phosphorylated YAPserine127, which may have contributed to increased satellite cell activation with reloading after HSU. These results indicate that voluntary wheel running increased YAP signaling and satellite cell activity after HSU and this was associated with improved recovery. NEW & NOTEWORTHY Although satellite cell involvement in muscle remodeling has been challenged, the data in this study suggest that voluntary wheel running increased satellite cell activity and suppressed Yes-associated protein (YAP) protein relative to no wheel running and this was associated with improved muscle recovery of force, fatigue resistance, expression of type I myosin heavy chain, and greater fiber cross-sectional area after disuse.


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