Abstract 12231: PECAM1 is Essential for Flow-mediated Gab1 Tyrosine Phosphorylation and Signaling in vitro and in vivo

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Suowen Xu ◽  
Marina Koroleva ◽  
Keigi Fujiwara ◽  
Zheng Gen Jin
Keyword(s):  
Tyrosine Phosphorylation ◽  
Wheel Running ◽  
Tyrosine Phosphatase ◽  
Common Mechanism ◽  
Membrane Localization ◽  
No Production ◽  
Voluntary Wheel Running ◽  
Voluntary Wheel

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

Effects of a high-fat diet and voluntary wheel running on gluconeogenesis and lipolysis in rats

1999 ◽  
Vol 86 (4) ◽  
pp. 1374-1380 ◽  
Author(s):  
Deborah A. Podolin ◽  
Yuren Wei ◽  
Michael J. Pagliassotti
Keyword(s):  
High Fat Diet ◽  
Corn Oil ◽  
Wheel Running ◽  
Whole Body ◽  
Free Access ◽  
Fat Pad ◽  
High Fat ◽  
Voluntary Wheel Running ◽  
Voluntary Wheel

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.

scholarly journals Tyrosine 425 within the activated erythropoietin receptor binds Syp, reduces the erythropoietin required for Syp tyrosine phosphorylation, and promotes mitogenesis

Blood ◽  
1996 ◽  
Vol 87 (11) ◽  
pp. 4495-4501 ◽  
Author(s):  
T Tauchi ◽  
JE Damen ◽  
K Toyama ◽  
GS Feng ◽  
HE Broxmeyer ◽  
...  
Keyword(s):  
Tyrosine Phosphorylation ◽  
Tyrosine Kinases ◽  
Intracellular Signaling ◽  
Tyrosine Phosphatase ◽  
Erythropoietin Receptor ◽  
Sh2 Domains ◽  
Proliferation And Differentiation ◽  
Stimulation Of

Erythropoietin (Epo), the primary in vivo stimulator of erythroid proliferation and differentiation, acts, in part, by altering the tyrosine phosphorylation levels of various intracellular signaling molecules. These phosphorylation levels are tightly regulated by both tyrosine kinases and tyrosine phosphatases. We have recently shown that the SH2 containing tyrosine phosphatase, Syp, binds directly to both the tyrosine phosphorylated form of the Epo receptor (EpoR) and to Grb2 after Epo stimulation of M07e cells engineered to express high levels of human EpoRs (T. Tauchi, et al: J Biol Chem 270:5631, 1995). To determine which tyrosine within the EpoR is responsible for binding Syp, we examined DA-3 cell lines expressing full-length mutant EpoRs bearing tyrosine to phenylalanine substitutions for each of the eight tyrosines within the intracellular domain of the EpoR. We found that: (1) all Epo-stimulated mutant EpoRs, except for the Y425F EpoR, coimmunoprecipitated with Syp; (2) all Epo-stimulated mutant EpoRs, except for the Y425F EpoR, bound to a GST-fusion protein containing both SH2 domains of Syp; (3) Jak2 could phosphorylate GST-Syp in vitro after Epo stimulation of wild-type (wt) EpoR expressing DA-3 cells; (4) Epo-stimulated tyrosine phosphorylation of Syp in vivo was markedly reduced in Y425F EpoR expressing DA-3 calls; and (5) DA-3 cells expressing the Y425F EpoR grow less well in response to Epo than wt EpoR expressing cells. These results suggest that Syp binds via its SH2 domains to phosphorylated Y425 within the EpoR and is then phosphorylated on tyrosine residues by Jak2. Moreover, Y425 in the EpoR reduces the Epo requirement for Syp tyrosine phosphorylation and promotes proliferation.

Identification and characterization of a high-affinity interaction between v-Crk and tyrosine-phosphorylated paxillin in CT10-transformed fibroblasts

1993 ◽  
Vol 13 (8) ◽  
pp. 4648-4656
Author(s):  
R B Birge ◽  
J E Fajardo ◽  
C Reichman ◽  
S E Shoelson ◽  
Z Songyang ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Tyrosine Phosphorylation ◽  
Cell Transformation ◽  
Tyrosine Phosphatase ◽  
State Level ◽  
Sh2 Domain ◽  
Sequence Specificity ◽  
Src Homology

The genome of avian sarcoma virus CT10 encodes a fusion protein in which viral Gag sequences are fused to cellular Crk sequences containing primarily Src homology 2 (SH2) and Src homology 3 (SH3) domains. Transformation of chicken embryo fibroblasts (CEF) with the Gag-Crk fusion protein results in the elevation of tyrosine phosphorylation on specific cellular proteins with molecular weights of 130,000, 110,000, and 70,000 (p130, p110, and p70, respectively), an event which has been correlated with cell transformation. In this study, we have identified the 70-kDa tyrosine-phosphorylated protein in CT10-transformed CEF (CT10-CEF) as paxillin, a cytoskeletal protein suggested to be important for organizing the focal adhesion. Tyrosine-phosphorylated paxillin was found to be complexed with v-Crk in vivo as evident from coimmunoprecipitation studies. Moreover, a bacterially expressed recombinant glutathione S-transferase (GST)-CrkSH2 fragment bound paxillin in vitro with a subnanomolar affinity, suggesting that the SH2 domain of v-Crk is sufficient for binding. Mapping of the sequence specificity of a GST-CrkSH2 fusion protein with a partially degenerate phosphopeptide library determined a motif consisting of pYDXP, and in competitive coprecipitation studies, an acetylated A(p)YDAPA hexapeptide was able to quantitatively inhibit the binding of GST-CrkSH2 to paxillin and p130, suggesting that it meets the minimal structural requirements necessary for the interaction of CrkSH2 with physiological targets. To investigate the mechanism by which v-Crk elevates the tyrosine phosphorylation of paxillin in vivo, we have treated normal CEF and CT10-CEF with sodium vanadate to inhibit protein tyrosine phosphatase activity. These data suggest that paxillin is involved in a highly dynamic kinase-phosphatase interplay in normal CEF and that v-Crk binding may interrupt this balance to increase the steady-state level of tyrosine phosphorylation. By contrast, the 130-kDa protein was not tyrosine phosphorylated upon vanadate treatment of normal CEF and only weakly affected in the CT10-CEF, suggesting that a different mechanism may be involved in its phosphorylation.

scholarly journals Dynamic Interaction of PTPμ with Multiple Cadherins In Vivo

1998 ◽  
Vol 141 (1) ◽  
pp. 287-296 ◽  
Author(s):  
Susann M. Brady-Kalnay ◽  
Tracy Mourton ◽  
Joseph P. Nixon ◽  
Gregory E. Pietz ◽  
Michael Kinch ◽  
...  
Keyword(s):  
Tyrosine Phosphorylation ◽  
Tyrosine Phosphatase ◽  
Cross Reactivity ◽  
Receptor Protein ◽  
Temperature Sensitive ◽  
Mutant Form ◽  
Cell Biol ◽  
E Cadherin

There is a growing body of evidence to implicate reversible tyrosine phosphorylation as an important mechanism in the control of the adhesive function of cadherins. We previously demonstrated that the receptor protein tyrosine phosphatase PTPμ associates with the cadherin–catenin complex in various tissues and cells and, therefore, may be a component of such a regulatory mechanism (Brady-Kalnay, S.M., D.L. Rimm, and N.K. Tonks. 1995. J. Cell Biol. 130:977– 986). In this study, we present further characterization of this interaction using a variety of systems. We observed that PTPμ interacted with N-cadherin, E-cadherin, and cadherin-4 (also called R-cadherin) in extracts of rat lung. We observed a direct interaction between PTPμ and E-cadherin after coexpression in Sf9 cells. In WC5 cells, which express a temperature-sensitive mutant form of v-Src, the complex between PTPμ and E-cadherin was dynamic, and conditions that resulted in tyrosine phosphorylation of E-cadherin were associated with dissociation of PTPμ from the complex. Furthermore, we have demonstrated that the COOH-terminal 38 residues of the cytoplasmic segment of E-cadherin was required for association with PTPμ in WC5 cells. Zondag et al. (Zondag, G., W. Moolenaar, and M. Gebbink. 1996. J. Cell Biol. 134: 1513–1517) have asserted that the association we observed between PTPμ and the cadherin–catenin complex in immunoprecipitates of the phosphatase arises from nonspecific cross-reactivity between BK2, our antibody to PTPμ, and cadherins. In this study we have confirmed our initial observation and demonstrated the presence of cadherin in immunoprecipitates of PTPμ obtained with three antibodies that recognize distinct epitopes in the phosphatase. In addition, we have demonstrated directly that the anti-PTPμ antibody BK2 that we used initially did not cross-react with cadherin. Our data reinforce the observation of an interaction between PTPμ and E-cadherin in vitro and in vivo, further emphasizing the potential importance of reversible tyrosine phosphorylation in regulating cadherin function.

scholarly journals Identification and characterization of a high-affinity interaction between v-Crk and tyrosine-phosphorylated paxillin in CT10-transformed fibroblasts.

1993 ◽  
Vol 13 (8) ◽  
pp. 4648-4656 ◽  
Author(s):  
R B Birge ◽  
J E Fajardo ◽  
C Reichman ◽  
S E Shoelson ◽  
Z Songyang ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Tyrosine Phosphorylation ◽  
Cell Transformation ◽  
Tyrosine Phosphatase ◽  
State Level ◽  
Sh2 Domain ◽  
Sequence Specificity ◽  
Src Homology

The genome of avian sarcoma virus CT10 encodes a fusion protein in which viral Gag sequences are fused to cellular Crk sequences containing primarily Src homology 2 (SH2) and Src homology 3 (SH3) domains. Transformation of chicken embryo fibroblasts (CEF) with the Gag-Crk fusion protein results in the elevation of tyrosine phosphorylation on specific cellular proteins with molecular weights of 130,000, 110,000, and 70,000 (p130, p110, and p70, respectively), an event which has been correlated with cell transformation. In this study, we have identified the 70-kDa tyrosine-phosphorylated protein in CT10-transformed CEF (CT10-CEF) as paxillin, a cytoskeletal protein suggested to be important for organizing the focal adhesion. Tyrosine-phosphorylated paxillin was found to be complexed with v-Crk in vivo as evident from coimmunoprecipitation studies. Moreover, a bacterially expressed recombinant glutathione S-transferase (GST)-CrkSH2 fragment bound paxillin in vitro with a subnanomolar affinity, suggesting that the SH2 domain of v-Crk is sufficient for binding. Mapping of the sequence specificity of a GST-CrkSH2 fusion protein with a partially degenerate phosphopeptide library determined a motif consisting of pYDXP, and in competitive coprecipitation studies, an acetylated A(p)YDAPA hexapeptide was able to quantitatively inhibit the binding of GST-CrkSH2 to paxillin and p130, suggesting that it meets the minimal structural requirements necessary for the interaction of CrkSH2 with physiological targets. To investigate the mechanism by which v-Crk elevates the tyrosine phosphorylation of paxillin in vivo, we have treated normal CEF and CT10-CEF with sodium vanadate to inhibit protein tyrosine phosphatase activity. These data suggest that paxillin is involved in a highly dynamic kinase-phosphatase interplay in normal CEF and that v-Crk binding may interrupt this balance to increase the steady-state level of tyrosine phosphorylation. By contrast, the 130-kDa protein was not tyrosine phosphorylated upon vanadate treatment of normal CEF and only weakly affected in the CT10-CEF, suggesting that a different mechanism may be involved in its phosphorylation.

scholarly journals Effect of Voluntary Wheel Running on Striatal Dopamine Level and Neurocognitive Behaviors after Molar Loss in Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Linlin Zhang ◽  
Yi Feng ◽  
Wenliang Ji ◽  
Jianzhang Liu ◽  
Kun Liu
Keyword(s):  
Physical Exercise ◽  
Wheel Running ◽  
Striatal Dopamine ◽  
Control Group ◽  
Dopamine Level ◽  
Sprague Dawley ◽  
Voluntary Wheel Running ◽  
Cognition And Emotion ◽  
Voluntary Wheel

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.

scholarly journals Comparison of changes in electrical activity, in isolated and in vivo hearts, induced by voluntary exercise in female rats

2020 ◽  
Author(s):  
Rachel Stones ◽  
Mark Drinkhill ◽  
Ed White
Keyword(s):  
Exercise Training ◽  
Electrical Activity ◽  
Wheel Running ◽  
Left Ventricular ◽  
Voluntary Exercise ◽  
Female Rats ◽  
Heart Weight ◽  
Voluntary Wheel Running ◽  
Voluntary Wheel

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.

scholarly journals Voluntary wheel running increases satellite cell abundance and improves recovery from disuse in gastrocnemius muscles from mice

2018 ◽  
Vol 124 (6) ◽  
pp. 1616-1628 ◽  
Author(s):  
Matthew J. Brooks ◽  
Ameena Hajira ◽  
Junaith S. Mohamed ◽  
Stephen E. Alway
Keyword(s):  
Satellite Cell ◽  
Cell Activation ◽  
Wheel Running ◽  
Cell Activity ◽  
Type I ◽  
Cross Sectional ◽  
Voluntary Wheel Running ◽  
Satellite Cell Activity ◽  
Voluntary Wheel

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.

scholarly journals Activation pattern of ACE2/Ang-(1–7) and ACE/Ang II pathway in course of heart failure assessed by multiparametric MRI in vivo in Tgαq*44 mice

2018 ◽  
Vol 124 (1) ◽  
pp. 52-65 ◽  
Author(s):  
Urszula Tyrankiewicz ◽  
Mariola Olkowicz ◽  
Tomasz Skórka ◽  
Magdalena Jablonska ◽  
Anna Orzylowska ◽  
...  
Keyword(s):  
Heart Failure ◽  
Wheel Running ◽  
Late Onset ◽  
Early Stage ◽  
Multiparametric Mri ◽  
Ang Ii ◽  
Voluntary Wheel Running ◽  
End Stage ◽  
Voluntary Wheel

Here, we analyzed systemic (plasma) and local (heart/aorta) changes in ACE/ACE-2 balance in Tgαq*44 mice in course of heart failure (HF). Tgαq*44 mice with cardiomyocyte-specific Gαq overexpression and late onset of HF were analyzed at different age for angiotensin pattern in plasma, heart, and aorta using liquid chromatography/mass spectrometry, for progression of HF by in vivo magnetic resonance imaging under isoflurane anesthesia, and for physical activity by voluntary wheel running. Six-month-old Tgαq*44 mice displayed decreased ventricle radial strains and impaired left atrial function. At 8–10 mo, Tgαq*44 mice showed impaired systolic performance and reduced voluntary wheel running but exhibited preserved inotropic reserve. At 12 mo, Tgαq*44 mice demonstrated a severe impairment of basal cardiac performance and modestly compromised inotropic reserve with reduced voluntary wheel running. Angiotensin analysis in plasma revealed an increase in concentration of angiotensin-(1–7) in 6- to 10-mo-old Tgαq*44 mice. However, in 12- to 14-mo-old Tgαq*44 mice, increased angiotensin II was noted with a concomitant increase in Ang III, Ang IV, angiotensin A, and angiotensin-(1–10). The pattern of changes in the heart and aorta was also compatible with activation of ACE2, followed by activation of the ACE pathway. In conclusion, mice with cardiomyocyte Gαq protein overexpression develop HF that is associated with activation of the systemic and the local ACE/Ang II pathway. However, it is counterbalanced by a prominent ACE2/Ang-(1–7) activation, possibly allowing to delay decompensation. NEW & NOTEWORTHY Changes in ACE/ACE-2 balance were analyzed based on measurements of a panel of nine angiotensins in plasma, heart, and aorta of Tgαq*44 mice in relation to progression of heart failure (HF) characterized by multiparametric MRI and exercise performance. The early stage of HF was associated with upregulation of the ACE2/angiotensin-(1–7) pathway, whereas the end-stage HF was associated with downregulation of ACE2/angiotensin-(1–7) and upregulation of the ACE/Ang II pathway. ACE/ACE-2 balance seems to determine the decompensation of HF in this model.

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 ◽  
...  
Keyword(s):  
Physical Activity ◽  
Genetic Model ◽  
Wheel Running ◽  
Ex Vivo ◽  
Hippocampal Volume ◽  
Antidepressant Effect ◽  
Spine Density ◽  
Voluntary Wheel Running ◽  
Voluntary Wheel

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.

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