application-consistent-massage-like-perturbations-on-mouse-calves

Application of Consistent Massage-Like Perturbations on Mouse Calves and Monitoring the Resulting Intramuscular Pressure Changes

Massage is generally recognized to be beneficial for relieving pain and inflammation. Although previous studies have reported anti-inflammatory effects of ...

application-passive-head-motion-to-generate-defined-accelerations-at

Application of Passive Head Motion to Generate Defined Accelerations at the Heads of Rodents

Exercise is widely recognized as effective for various diseases and physical disorders, including those related to brain dysfunction. However, molecular ...

National Rehabilitation Center for Persons with disabilities

Moderate mechanical stress generated by normal joint loading and movement is essential for the maintenance of healthy articular cartilage. However, the effects of reduced loading caused by the absence of weight bearing or joint motion on articular cartilage and subchondral bone is still poorly understood. We aimed to characterize morphological and metabolic responses of articular cartilage and subchondral bone to decreased mechanical stress in vivo.

Thinning of articular cartilage after joint unloading or immobilization. An experimental investigation of the pathogenesis in mice.

Physical inactivity gives rise to numerous diseases and organismal dysfunctions, particularly those related to aging. Musculoskeletal disorders including muscle atrophy, which can result from a sedentary lifestyle, aggravate locomotive malfunction and evoke a vicious circle leading to severe functional disruptions of vital organs such as the brain and cardiovascular system. Although the significance of physical activity is evident, molecular mechanisms behind its beneficial effects are poorly understood. Here, we show that massage-like mechanical interventions modulate immobilization-induced pro-inflammatory responses of macrophages  and alleviate muscle atrophy. Local cyclical compression (LCC) on mouse calves, which generates intramuscular pressure waves with amplitude of 50 mmHg, partially restores the myofiber thickness and contracting forces of calf muscles that are decreased by hindlimb immobilization. LCC tempers the increase in the number of cells expressing pro-inflammatory proteins, tumor necrosis factor-α and monocyte chemoattractant protein-1 (MCP-1), including macrophages  The reversing effect of LCC on immobilization-induced thinning of myofibers is almost completely nullified when macrophages recruited from circulating blood are depleted by administration of clodronate liposomes. Furthermore, application of pulsatile fluid shear stress, but not hydrostatic pressure, reduces the expression of MCP-1 in macrophages  Together with the LCC-induced movement of intramuscular interstitial fluid detected by µCT analysis, these results suggest that mechanical modulation of macrophage function is involved in physical inactivity-induced muscle atrophy and inflammation. Our findings uncover the implication of mechanosensory function of macrophages in disuse muscle atrophy, thereby opening a new path to develop a novel therapeutic strategy utilizing mechanical interventions.

Local cyclical compression modulates macrophage function  and alleviates immobilization-induced muscle atrophy.

Mechanical forces are known to be involved in various biological processes. However, it remains unclear whether brain functions are mechanically regulated under physiological conditions. Here, we demonstrate that treadmill running and passive head motion (PHM), both of which produce mechanical impact on the head, have similar effects on the hallucinogenic 5-hydroxytryptamine (5-HT) receptor subtype 2A (5-HT) signaling in the prefrontal cortex (PFC) of rodents. PHM generates interstitial fluid movement that is estimated to exert shear stress of a few pascals on cells in the PFC. Fluid shear stress of a relevant magnitude on cultured neuronal cells induces ligand-independent internalization of 5-HT receptor, which is observed in mouse PFC neurons after treadmill running or PHM. Furthermore, inhibition of interstitial fluid movement by introducing polyethylene glycol hydrogel eliminates the effect of PHM on 5-HT receptor signaling in the PFC. Our findings indicate that neuronal cell function can be physiologically regulated by mechanical forces in the brain.

ArticleTotal : 2	Year
Publication title Cited by 5	2019
Publication title Cited by 1	2022

Article	Year
Thinning of articular cartilage after joint unloading or immobilization. An experimental investigation of the pathogenesis in mice. Osteoarthritis and cartilage\| PubMed ID: 27916560	2017
Local cyclical compression modulates macrophage function and alleviates immobilization-induced muscle atrophy. Clinical science (London, England : 1979)\| PubMed ID: 30209036	2018
Mechanical Regulation Underlies Effects of Exercise on Serotonin-Induced Signaling in the Prefrontal Cortex Neurons. iScience\| PubMed ID: 32062453	2020

Naoyoshi Sakitani

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