Effect of physical exercise on brain and lipid metabolism in mouse models of multiple sclerosis

Multiple sclerosis (MS) is a neurodegenerative, demyelinating, and chronic inflammatory disease characterized by central nervous system (CNS) lesions that lead to high levels of disability and severe physical and cognitive disturbances. Conventional therapies are not enough to control the neuroinflammatory process in MS and are not able to inhibit ongoing damage to the CNS. Thus, the secretome of mesenchymal stem cells (MSC-S) has been postulated as a potential therapy that could mitigate symptoms and disease progression. We considered that its combination with physical exercise (EX) could induce superior effects and increase the MSC-S effectiveness in this condition. Recent studies have revealed that both EX and MSC-S share similar mechanisms of action that mitigate auto-reactive T cell infiltration, regulate the local inflammatory response, modulate the proinflammatory profile of glial cells, and reduce neuronal damage. Clinical and experimental studies have reported that these treatments in an isolated way also improve myelination, regeneration, promote the release of neurotrophic factors, and increase the recruitment of endogenous stem cells. Together, these effects reduce disease progression and improve patient functionality. Despite these results, the combination of these methods has not yet been studied in MS. In this review, we focus on molecular elements and cellular responses induced by these treatments in a separate way, showing their beneficial effects in the control of symptoms and disease progression in MS, as well as indicating their contribution in clinical fields. In addition, we propose the combined use of EX and MSC-S as a strategy to boost their reparative and immunomodulatory effects in this condition, combining their benefits on synaptogenesis, neurogenesis, remyelination, and neuroinflammatory response. The findings here reported are based on the scientific evidence and our professional experience that will bring significant progress to regenerative medicine to deal with this condition.

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Homotaurine, a safe blood-brain barrier permeable GABAA-R-specific agonist, ameliorates disease in mouse models of multiple sclerosis

Scientific Reports ◽

10.1038/s41598-018-32733-3 ◽

2018 ◽

Vol 8 (1) ◽

Cited By ~ 5

Author(s):

Jide Tian ◽

Hoa Dang ◽

Martin Wallner ◽

Richard Olsen ◽

Daniel L. Kaufman

Keyword(s):

Multiple Sclerosis ◽

Blood Brain Barrier ◽

Mouse Models ◽

Brain Barrier ◽

Blood Brain ◽

Safe Blood

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Effects of Long Lasting Physical Exercise and Training on Lipid Metabolism

Metabolic Adaptation to Prolonged Physical Exercise ◽

10.1007/978-3-0348-5523-5_20 ◽

1975 ◽

pp. 156-193 ◽

Cited By ~ 18

Author(s):

P. Paul

Keyword(s):

Lipid Metabolism ◽

Physical Exercise ◽

Exercise And Training ◽

And Training

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PTRF/Cavin1 remodels phospholipid metabolism to promote tumor proliferation and suppress immune responses in glioblastoma by stabilizing cPLA2

Neuro-Oncology ◽

10.1093/neuonc/noaa255 ◽

2020 ◽

Author(s):

Kaikai Yi ◽

Qi Zhan ◽

Qixue Wang ◽

Yanli Tan ◽

Chuan Fang ◽

...

Keyword(s):

Lipid Metabolism ◽

Immune Responses ◽

Molecular Mechanism ◽

Mouse Models ◽

Phospholipid Composition ◽

Tumor Infiltrating Lymphocytes ◽

Intracranial Tumor ◽

Tumor Proliferation

Abstract Background Metabolism remodeling is a hallmark of glioblastoma (GBM) that regulates tumor proliferation and the immune microenvironment. Previous studies have reported that increased polymerase 1 and transcript release factor (PTRF) levels are associated with a worse prognosis in glioma patients. However, the biological role and the molecular mechanism of PTRF in GBM metabolism remain unclear. Methods The relationship between PTRF and lipid metabolism in GBM was detected by non-targeted metabolomics profiling and subsequent lipidomics analysis. Western blotting, qRT-PCR, and immunoprecipitation were conducted to explore the molecular mechanism of PTRF in lipid metabolism. A sequence of in vitro and in vivo experiments (both xenograft tumor and intracranial tumor mouse models) were used to detect the tumor-specific impacts of PTRF. Results Here, we show that PTRF triggers a cytoplasmic phospholipase A2 (cPLA2)-mediated phospholipid remodeling pathway that promotes GBM tumor proliferation and suppresses tumor immune responses. Research in primary cell lines from GBM patients revealed that cells overexpressing PTRF show increased cPLA2 activity —resulting from increased protein stability —and exhibit remodeled phospholipid composition. Subsequent experiments revealed that PTRF overexpression alters the endocytosis capacity and energy metabolism of GBM cells. Finally, in GBM xenograft and intracranial tumor mouse models, we showed that inhibiting cPLA2 activity blocks tumor proliferation and prevents PTRF-induced reduction in CD8 + tumor-infiltrating lymphocytes. Conclusions The PTRF-cPLA2 lipid remodeling pathway promotes tumor proliferation and suppresses immune responses in GBM. In addition, our findings highlight multiple new therapeutic targets for GBM.

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