Modified forelimb grip strength test detects aging-associated physiological decline in skeletal muscle function in male mice

Takeshita, Hikari; Yamamoto, Kōichi; Nozato, Satoko; Inagaki, Takuya; Tsuchimochi, Hirotsugu; Shirai, Masamitsu; Yamamoto, Ryohei; Imaizumi, Yuki; Hongyo, Kazuhiro; Yokoyama, Serina; Takeda, Masao; Oguro, Ryosuke; Takami, Yoichi; Itoh, Noriyuki; Takeya, Yasushi; Sugimoto, Ken; Fukada, So‐ichiro; Rakugi, Hiromi

doi:10.1038/srep42323

Cited by 171 publications

(129 citation statements)

References 32 publications

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“…In our study, we measured the grip strength of individual forepaws that we believe has increased the sensitivity of the test. Additionally, it has been reported that the grip strength test can detect ageing-associated decline in skeletal muscle function in the mouse [68] suggesting that when using this test, the age of the animals needs to be taken under consideration. Indeed, we have recently demonstrated full recovery of grip strength within 3 weeks in young mice after focal ischemia [41], while in this study in middle-aged mice, even at 6 weeks after tMCAO the grip strength did not fully recover.…”

Section: Discussionmentioning

confidence: 99%

Obesity-induced type 2 diabetes impairs neurological recovery after stroke in correlation with decreased neurogenesis and persistent atrophy of parvalbumin-positive interneurons

et al. 2019

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Type 2 diabetes (T2D) hampers stroke recovery though largely undetermined mechanisms. Few preclinical studies have investigated the effect of genetic/toxin-induced diabetes on long-term stroke recovery. However, the effects of obesity-induced T2D are mostly unknown. We aimed to investigate whether obesity-induced T2D worsens long-term stroke recovery through the impairment of brain’s self-repair mechanisms – stroke-induced neurogenesis and parvalbumin (PV)+ interneurons-mediated neuroplasticity. To mimic obesity-induced T2D in the middle-age, C57bl/6j mice were fed 12 months with high-fat diet (HFD) and subjected to transient middle cerebral artery occlusion (tMCAO). We evaluated neurological recovery by upper-limb grip strength at 1 and 6 weeks after tMCAO. Gray and white matter damage, stroke-induced neurogenesis, and survival and potential atrophy of PV-interneurons were quantitated by immunohistochemistry (IHC) at 2 and 6 weeks after tMCAO. Obesity/T2D impaired neurological function without exacerbating brain damage. Moreover, obesity/T2D diminished stroke-induced neural stem cell (NSC) proliferation and neuroblast formation in striatum and hippocampus at 2 weeks after tMCAO and abolished stroke-induced neurogenesis in hippocampus at 6 weeks. Finally, stroke resulted in the atrophy of surviving PV-interneurons 2 weeks after stroke in both non-diabetic and obese/T2D mice. However, after 6 weeks, this effect selectively persisted in obese/T2D mice. We show in a preclinical setting of clinical relevance that obesity/T2D impairs neurological functions in the stroke recovery phase in correlation with reduced neurogenesis and persistent atrophy of PV-interneurons, suggesting impaired neuroplasticity. These findings shed light on the mechanisms behind impaired stroke recovery in T2D and could facilitate the development of new stroke rehabilitative strategies for obese/T2D patients.

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Section: Discussionmentioning

confidence: 99%

Obesity-induced type 2 diabetes impairs neurological recovery after stroke in correlation with decreased neurogenesis and persistent atrophy of parvalbumin-positive interneurons

et al. 2019

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“…We also could not detect any phenotypic differences in tissue weight itself or insulin signaling intensity in skeletal muscle between WT and MYOF KO mice. In addition, muscle function, as assessed by the forelimb grip strength method developed by us, 31 was comparable between WT and MYOF KO mice (data not shown).…”

Section: Discussionmentioning

confidence: 87%

Novel properties of myoferlin in glucose metabolism via pathways involving modulation of adipose functions

et al. 2020

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While adipose tissue is required to maintain glucose metabolism, excessive calorie intake induces obesity via mechanisms including accelerated proliferation and differentiation of preadipocytes, leading to insulin resistance. Here, we investigated the role of myoferlin (MYOF), a ferlin family protein, in regulating glucose metabolism by mainly focusing on its unknown role in adipose tissue. Whereas young MYOF knockout (KO) mice on a normal diet showed aggravated glucose tolerance and insulin sensitivity, those on a high-fat diet (HFD) showed preserved glucose tolerance with an attenuated gain of body weight, reduced visceral fat deposits, and less severe fatty liver. The Adipose MYOF expression was reduced by aging but was restored by an HFD along with the retained expression of NFAT transcription factors. Lossof-function of MYOF in preadipocytes suppressed proliferation and differentiation into mature adipocytes along with the decreased expression of genes involved in adipogenesis. The MYOF expression in preadipocytes was reduced with differentiation. Attenuated obesity in MYOF KO mice on an HFD was also accompanied with increased oxygen consumption by an unidentified mechanism and with reduced adipose inflammation due to less inflammatory macrophages. These insights suggest that the multifunctional roles of MYOF involve the regulation of preadipocyte function and affect glucose metabolism bidirectionally depending on consumed calories. K E Y W O R D Sadipocyte differentiation, insulin resistance, myoferlin, obesity | 2793 NOZATO eT Al.

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“…The gauge was placed horizontally for all-limbs tests and vertically for forelimb tests. As mice were placed on a grid for the all-limbs test or grasped a bar for the forelimb test, mice's tails were slowly pulled backwards or downwards 3-5 times to record the peak tension at the time that the mice released their paws (28). All tests were repeated thrice at 30 min intervals, and the average of 3 values was used for calculations.…”

Section: Grip Testmentioning

confidence: 99%

Magnolol Attenuates Cisplatin-Induced Muscle Wasting by M2c Macrophage Activation

et al. 2020

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Cancer chemotherapy induces sarcopenia, which is a rapid loss of muscle mass that directly restricts daily activities and leads to poor quality of life and increased mortality. Although hormone-related therapies have been used to improve appetite and nutritional status, current treatments are considered palliative. Thus, the protection of skeletal muscle loss without adverse effects is essential to allow the maintenance of chemotherapy in cancer patients. Magnolol from Magnolia officinalis has several pharmacological effects including anti-cancer and anti-inflammatory activities, but the protection from muscle atrophy is not well-understood. In the present study, we investigated the effects of magnolol on muscle wasting and macrophage subtypes in a cisplatin-induced sarcopenia mouse model. We showed that magnolol significantly attenuated the body weight and the muscle loss induced by cisplatin injection. The diameter of the tibialis anterior muscle was markedly increased after magnolol treatment in cisplatin-treated mice. Importantly, magnolol increased macrophage infiltration into skeletal muscle while not affecting proliferation of macrophages. Magnolol attenuated the imbalance of M1/M2c macrophages by increasing CD206 + CD163 + M2c tissue reparative macrophages. Further, magnolol increased insulin-like growth factor (IGF)-1 expression. This effect was also observed in bone marrow-derived macrophages upon magnolol treatment. Taken together, magnolol may be a promising chemoprotective agent for the prevention of muscle atrophy through the upregulating M2c macrophages, which are a major source of IGF-1.

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Modified forelimb grip strength test detects aging-associated physiological decline in skeletal muscle function in male mice

Cited by 171 publications

References 32 publications

Obesity-induced type 2 diabetes impairs neurological recovery after stroke in correlation with decreased neurogenesis and persistent atrophy of parvalbumin-positive interneurons

Obesity-induced type 2 diabetes impairs neurological recovery after stroke in correlation with decreased neurogenesis and persistent atrophy of parvalbumin-positive interneurons

Novel properties of myoferlin in glucose metabolism via pathways involving modulation of adipose functions

Magnolol Attenuates Cisplatin-Induced Muscle Wasting by M2c Macrophage Activation

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