Overexpression of mini‐agrin in skeletal muscle increases muscle integrity and regenerative capacity in laminin‐α2‐deficient mice

Low levels of the neurotransmitter serotonin have been associated with the onset of depression. While traditional treatments include antidepressants, physical exercise has emerged as an alternative for patients with depressive disorders. Yet there remains the fundamental question of how exercise is sensed by the brain. The existence of a muscle–brain endocrine loop has been proposed: according to this scenario, exercise modulates metabolization of tryptophan into kynurenine within skeletal muscle, which in turn affects the brain, enhancing resistance to depression. But the breakdown of tryptophan into kynurenine during exercise may also alter serotonin synthesis and help limit depression. In this study, we investigated whether peripheral serotonin might play a role in muscle–brain communication permitting adaptation for endurance training. We first quantified tryptophan metabolites in the blood of 4 trained athletes before and after a long-distance trail race and correlated changes in tryptophan metabolism with physical performance. In parallel, to assess exercise capacity and endurance in trained control and peripheral serotonin–deficient mice, we used a treadmill incremental test. Peripheral serotonin–deficient mice exhibited a significant drop in physical performance despite endurance training. Brain levels of tryptophan metabolites were similar in wild-type and peripheral serotonin–deficient animals, and no products of muscle-induced tryptophan metabolism were found in the plasma or brains of peripheral serotonin–deficient mice. But mass spectrometric analyses revealed a significant decrease in levels of 5-hydroxyindoleacetic acid (5-HIAA), the main serotonin metabolite, in both the soleus and plantaris muscles, demonstrating that metabolization of tryptophan into serotonin in muscles is essential for adaptation to endurance training. In light of these findings, the breakdown of tryptophan into peripheral but not brain serotonin appears to be the rate-limiting step for muscle adaptation to endurance training. The data suggest that there is a peripheral mechanism responsible for the positive effects of exercise, and that muscles are secretory organs with autocrine-paracrine roles in which serotonin has a local effect.

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Slow-Adhering Stem Cells Derived from Injured Skeletal Muscle Have Improved Regenerative Capacity

American Journal Of Pathology ◽

10.1016/j.ajpath.2011.05.004 ◽

2011 ◽

Vol 179 (2) ◽

pp. 931-941 ◽

Cited By ~ 8

Author(s):

Xiaodong Mu ◽

Guosheng Xiang ◽

Christopher R. Rathbone ◽

Haiying Pan ◽

Ian H. Bellayr ◽

...

Keyword(s):

Skeletal Muscle ◽

Stem Cells ◽

Regenerative Capacity

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Novel metabolic disorders in skeletal muscle of Lipodystrophic Bscl2/Seipin deficient mice

Molecular and Cellular Endocrinology ◽

10.1016/j.mce.2018.12.001 ◽

2019 ◽

Vol 482 ◽

pp. 1-10 ◽

Cited By ~ 3

Author(s):

Wenqiong Xu ◽

Hongyi Zhou ◽

Hongzhuan Xuan ◽

Pradip Saha ◽

Gongxian Wang ◽

...

Keyword(s):

Skeletal Muscle ◽

Metabolic Disorders ◽

Deficient Mice

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Comparative gene expression and phenotype analyses of skeletal muscle from aged wild-type and PAPP-A-deficient mice

Experimental Gerontology ◽

10.1016/j.exger.2016.04.005 ◽

2016 ◽

Vol 80 ◽

pp. 36-42 ◽

Cited By ~ 6

Author(s):

Cheryl A. Conover ◽

Laurie K. Bale ◽

K. Sreekumaran Nair

Keyword(s):

Gene Expression ◽

Skeletal Muscle ◽

Wild Type ◽

Deficient Mice

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Treadmill running causes significant fiber damage in skeletal muscle of KATP channel-deficient mice

Physiological Genomics ◽

10.1152/physiolgenomics.00064.2005 ◽

2005 ◽

Vol 22 (2) ◽

pp. 204-212 ◽

Cited By ~ 31

Author(s):

M. Thabet ◽

T. Miki ◽

S. Seino ◽

J.-M. Renaud

Keyword(s):

Skeletal Muscle ◽

Muscle Fibers ◽

Treadmill Running ◽

Wild Type ◽

Connective Tissues ◽

Fiber Damage ◽

Hindlimb Muscles ◽

Skeletal Muscle Fibers ◽

And Function ◽

Deficient Mice

Although it has been suggested that the ATP-sensitive K+ (KATP) channel protects muscle against function impairment, most studies have so far given little evidence for significant perturbation in the integrity and function of skeletal muscle fibers from inactive mice that lack KATP channel activity in their cell membrane. The objective was, therefore, to test the hypothesis that KATP channel-deficient skeletal muscle fibers become damaged when mice are subjected to stress. Wild-type and KATP channel-deficient mice (Kir6.2−/− mice) were subjected to 4–5 wk of treadmill running at either 20 m/min with 0° inclination or at 24 m/min with 20° uphill inclination. Muscles of all wild-type mice and of nonexercised Kir6.2−/− mice had very few fibers with internal nuclei. After 4–5 wk of treadmill running, there was little evidence for connective tissues and mononucleated cells in Kir6.2−/− hindlimb muscles, whereas the number of fibers with internal nuclei, which appear when damaged fibers are regenerated by satellite cells, was significantly higher in Kir6.2−/− than wild-type mice. Between 5% and 25% of the total number of fibers in Kir6.2−/− extensor digitum longus, plantaris, and tibialis muscles had internal nuclei, and most of such fibers were type IIB fibers. Contrary to hindlimb muscles, diaphragms of Kir6.2−/− mice that had run at 24 m/min had few fibers with internal nuclei, but mild to severe fiber damage was observed. In conclusion, the study provides for the first time evidence 1) that the KATP channels of skeletal muscle are essential to prevent fiber damage, and thus muscle dysfunction; and 2) that the extent of fiber damage is greater and the capacity of fiber regeneration is less in Kir6.2−/− diaphragm muscles compared with hindlimb muscles.

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