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Project description:Skeletal muscle has gained recognition as an endocrine organ releasing myokines upon contraction during physical exercise. These myokines exert both local and pleiotropic health benefits, underscoring the crucial role of muscle function in countering obesity and contributing to the overall positive effects of exercise on health. Here, we found that exercise activates muscle p38γ, increasing locomotor activity through the secretion of interleukin-15 (IL-15). IL-15 signals in the motor cortex, stimulating locomotor activity. This activation of muscle p38γ, leading to an increase locomotor activity, plays a crucial role in reducing the risk of diabetes and liver steatosis, unveiling a vital muscle-brain communication pathway with profound clinical implications. The correlation between p38γ activation in human muscle during acute exercise and increased blood IL-15 levels highlights the potential therapeutic relevance of this pathway in treating obesity and metabolic diseases. These findings provide valuable insights into the molecular basis of exercise-induced myokine responses promoting physical activity.
| S-EPMC11323882 | biostudies-literature
Project description:Remodeling p38 signaling in muscle controls locomotor activity via IL-15
| PRJNA1099905 | ENA
Project description:Aging reduces locomotor capacity. Although a decrease in the activity of the nigrostriatal dopamine (DA) system is one of key mechanisms linked to the drop-in locomotor activity in aging, the specific molecule responsible for controlling this decline remains elusive. Here we report that sirtuin 3 (SIRT3), a mitochondrial deacetylase associated with an anti-aging effect, is downregulated in nigral DA neurons of 20-month-old mice, showing the decline in locomotor activity, and that the declined locomotor activity by aging was deteriorated with more serious alteration in the levels of mitochondria-related proteins in mice with genetic deletion of SIRT3 compared to age-matched control mice. Moreover, SIRT3 upregulation through the administration of adeno-associated virus serotype 1 (AAV1) encoding the SIRT3 gene in the substantia nigra (SN) mitigated the age-dependent loss of locomotor activity by the preservation of the nigrostriatal DA system from aging in vivo. Therefore, we conclude that SIRT3 preservation in the nigrostriatal DA system has resistance to age-related locomotor decline, suggesting that SIRT3 upregulation in nigral DA neurons can be useful to preserve locomotor capacity in aging.
2024-12-31 | GSE246388 | GEO
Project description:Introduction: Advanced maternal age (AMA) increases the risk of pregnancy complications, in part due to impaired placentation. While exercise during pregnancy can improve outcomes, its potential to mitigate the effects of AMA has not been investigated. We evaluated the impact of exercise in a mouse model of AMA. Methods: Females were paired with males at 9 or 34 weeks of age, with one group of aged females having access to running wheels four weeks prior to and during pregnancy. Pregnant females (N = 19 per group) were collected at gestational day (GD) 11.5. Placentas were collected for RNA sequencing (N = 17-20 per group). Results: Aged females without access to running wheels had heavier fat depots, while those with access to running wheels did not differ from young females. The number of viable conceptuses and fetal size were lower in both groups of aged females. Hundreds of genes were differentially expressed between young females and each of the aged groups, but only one gene was affected by access to running wheels. The placental transcriptomes of both aged groups were more similar to that of young mice at GD 10.5 than to young mice at GD 11.5, suggesting delayed placental development. Conclusions: Our model reproduced previously-reported effects of age on fetal development and placental transcriptomics, but these were not mitigated by increased voluntary locomotor activity, despite a reduction in adiposity. Remarkably, increased voluntary locomotor activity had almost no effects on placental gene expression in aged mice.
2025-05-10 | GSE280473 | GEO
Project description:Spinal cord injury (SCI) is one of the most disabling health problems facing adults today. Locomotor training has been shown to induce substantial recovery in muscle size and muscle function in both transected and contusion injury animal models of SCI. The overall objective of this study is to implement genome wide expression profiling of skeletal muscle to define the molecular pathways associated with muscle remodeling after SCI and during locomotor training (TM). We profiled rat soleus of total 36 samples including controls; 3, 8 and 14 days after SCI; 8 and 14 days after SCI with locomotor treadmill training (TM).
2015-06-30 | E-GEOD-45550 | biostudies-arrayexpress
Project description:Evidence implicating p38γ and p38δ (p38γ/p38δ) in inflammation are mainly based on experiments using p38γ/p38δ deficient (p38γ/δ-/-) mice, which show low levels of TPL2, the kinase upstream of MKK1-ERK1/2 in myeloid cells. This could obscure p38γ/p38δ roles, since TPL2 is essential for regulating inflammation. Here we generated a p38γD171A/D171A/p38δ-/- (p38γ/δKIKO) mouse, expressing kinase-inactive p38γ and lacking p38δ. This mouse exhibited normal TPL2 levels, making it an excellent tool to elucidate specific p38γ/p38δ functions. p38γ/δKIKO mice showed a reduced inflammatory response and less susceptibility to LPS-induced septic shock and Candida albicans infection than wild-type mice. Gene expression analyses in LPS-activated WT and p38γ/δKIKO macrophages revealed that p38γ/p38δ regulated numerous genes implicated in innate immune response.
2023-08-09 | GSE234776 | GEO
Project description:Traumatic spinal cord injury (SCI) often leads to loss of locomotor function. Neuroplasticity of spinal circuitry underlies some functional recovery and therefore represents a therapeutic target to improve locomotor function following SCI. However, the cellular and molecular mechanisms mediating neuroplasticity below the lesion level are not fully understood. The present study performed a gene expression profiling in the rat lumbar spinal cord at 1 and 3 weeks after contusive SCI at T9 compared to control rat that received sham injury (laminectomy). The below-level gene expression profiles were compared with those of animals that were subjected to treadmill locomotor training. Rat lumbar spinal cords were taken for the microarray analysis at 1 and 3 weeks after contusive spinal cord injury at the T9 level. Another group of rats received treadmill locomotor training for 3 weeks, and theirs spinal cords were harvested for the microarray. The changes in gene expression after spinal cord injury were analyzed at the two time points. The influence of treadmill locomotor training was evaluated by comparing gene expression profiles between animals with or without treadmill training.
2013-11-27 | E-GEOD-52763 | biostudies-arrayexpress
Project description:The advent of immune checkpoint blockade has improved patient outcomes, providing durable disease control by reversing localized tumor-mediated immune-suppression and promoting anti-tumor immunity. Despite successes in melanoma and lung cancer, these therapies have largely failed in pancreatic ductal adenocarcinoma (PDA); a ‘cold’ tumor with the highest mortality rate among all major cancers. PDA is uniquely characterized by multiple intra-pancreatic tumor- and stroma-induced mechanisms of immune-suppression, and there remains a great need to explore creative approaches to improve anti-tumor immune responses in this disease. Herein, we show routine aerobic exercise provides tumor-protective benefits in murine PDA through modulation of both systemic and intra-tumoral immunity. Reversing immune-suppressive properties of both myeloid and T cell populations, we found the anti-tumor benefits of exercise require CD8 T cell activation and expansion in the tumor. Specifically, we report the sub-population of IL15Ra+ CD8 T cells is required for exercise-induced tumor protection and anti-tumor immunity, both of which are abrogated in the context IL-15 blockade. We further show that exercise-induced increases in intra-tumoral T cells are governed by adrenergic signaling and S1P-gradient dependent lymphocyte migration. Finally, we found that combination with aerobic exercise sensitizes pancreatic tumors to anti-PD-1 therapy. Overall, our work highlights the unique mechanisms governing exercise-induced tumor protection in PDA, and uncovers the importance of the interplay between systemic and intra-tumoral immunity to develop innovative strategies to reverse immune-suppression in this devastating disease.
2022-05-11 | GSE176311 | GEO
Project description:Mammalian and fish pineals play a key role in adapting behaviour to the ambient light conditions through the release of melatonin. In mice, light inhibits nocturnal locomotor activity via the nonvisual photoreceptor Melanopsin. In contrast to the extensively studied function of Melanopsin in the indirect regulation of the rodent pineal, its role in the intrinsically photosensitive zebrafish pineal has not been elucidated. Therefore, it is not evident if the light signalling mechanism is conserved between distant vertebrates, and how Melanopsin could affect diurnal behaviour. A double knockout of melanopsins (opn4.1-opn4xb) was generated in the diurnal zebrafish, which manifests attenuated locomotor activity during the wake state. Transcriptome sequencing gave insight into pathways downstream of Melanopsin, implying that sustained repression of the melatonin pathway is required to elevate locomotor activity during the diurnal wake state. Moreover, we show that light induces locomotor activity during the diurnal wake state in an intensity-dependent manner. These observations suggest a common Melanopsin-driven mechanism between zebrafish and mammals, while the diurnal and nocturnal chronotypes are inversely regulated downstream of melatonin.
2021-12-06 | GSE189906 | GEO
Project description:We exploited the extraordinary ecomorphological diversity of squamates to assess brain phenotypic diversification with respect to locomotor specialization, by integrating transcriptomic data along with other methods. We reveal significant changes in cerebellar morphology as well as dynamic gene expression that all correlate with locomotor behaviours.
2019-11-07 | GSE139570 | GEO