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Conditioned media from AICAR-treated skeletal muscle cells increases neuronal differentiation of adult neural progenitor cells.

ABSTRACT: Exercise has profound benefits for brain function in animals and humans. In rodents, voluntary wheel running increases the production of new neurons and upregulates neurotrophin levels in the hippocampus, as well as improving synaptic plasticity, memory function and mood. The underlying cellular mechanisms, however, remain unresolved. Recent research indicates that peripheral organs such as skeletal muscle, liver and adipose tissue secrete factors during physical activity that may influence neuronal function. Here we used an in vitro cell assay and proteomic analysis to investigate the effects of proteins secreted from skeletal muscle cells on adult hippocampal neural progenitor cell (aNPC) differentiation. We also sought to identify the relevant molecules driving these effects. Specifically, we treated rat L6 skeletal muscle cells with the AMP-kinase (AMPK) agonist 5-aminoimidazole-4-carboxamide-1-?-d-ribofuranoside (AICAR) or vehicle (distilled water). We then collected the conditioned media (CM) and fractionated it using high-performance liquid chromatography (HPLC). Treatment of aNPCs with a specific fraction of the AICAR-CM upregulated expression of doublecortin (DCX) and Tuj1, markers of immature neurons. Proteomic analysis of this fraction identified proteins known to be involved in energy metabolism, cell migration, adhesion and neurogenesis. Culturing differentiating aNPCs in the presence of one of the factors, glycolytic enzyme glucose-6-phosphate isomerase (GPI), or AICAR-CM, increased the proportion of neuronal (Tuj1+) and astrocytic, glial fibrillary acidic protein (GFAP+) cells. Our study provides further evidence that proteins secreted from skeletal muscle cells may serve as a critical communication link to the brain through factors that enhance neural differentiation.

SUBMITTER: Moon HY

PROVIDER: S-EPMC6364830 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Conditioned media from AICAR-treated skeletal muscle cells increases neuronal differentiation of adult neural progenitor cells.

Moon Hyo Youl HY Javadi Sahar S Stremlau Matthew M Yoon Kyeong Jin KJ Becker Benjamin B Kang Sung-Ung SU Zhao Xinyu X van Praag Henriette H

Neuropharmacology 20181102 Pt A

Exercise has profound benefits for brain function in animals and humans. In rodents, voluntary wheel running increases the production of new neurons and upregulates neurotrophin levels in the hippocampus, as well as improving synaptic plasticity, memory function and mood. The underlying cellular mechanisms, however, remain unresolved. Recent research indicates that peripheral organs such as skeletal muscle, liver and adipose tissue secrete factors during physical activity that may influence neur ...[more]

PMID: 30391731

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Project description:INTRODUCTION:Reduced number and activities of epidermal stem cells are related to the features of photoaged skin. It was reported that conditioned media from various stem cell cultures are capable of improving the signs of cutaneous aging. This work was performed to establish epidermal progenitor cells derived from mesenchymal stem cells, and to evaluate the anti-aging efficacy of its conditioned media. METHODS:Epidermal progenitor cell culture was established by differentiation from mesenchymal stem cells, and its conditioned medium (EPC-CM) was prepared. Normal human dermal fibroblasts were exposed to hydrogen peroxide and the protective effects of EPC-CM were investigated, monitoring intracellular reactive oxygen species (ROS), cellular defense enzymes, collagen biosynthesis, and mitogen-associated protein kinase (MAPK) signaling. Anti-aging efficacy of cosmetic essence (5% EPC-CM) was evaluated by a clinical test with 25 Korean women aged between 29 and 69. RESULTS:Hydrogen peroxide hindered proliferation of fibroblasts and increased the levels of intracellular ROS. Pretreatment of EPC-CM protected fibroblasts from oxidative stress as shown by accelerated proliferation and reduced ROS generation. EPC-CM effectively prevented hydrogen peroxide-induced alterations of the activities, as well as mRNA and protein levels, of antioxidative enzymes, such as superoxide dismutase, catalase, and glutathione peroxidase. Reduced type I collagen biosynthesis and stimulated phosphorylation of MAPK signaling proteins, induced by oxidative damage, were also prevented by EPC-CM. In clinical study, wrinkle, depression, and skin texture were improved by the topical application of a formulation containing 5% EPC-CM within 4 weeks. CONCLUSION:Epidermal progenitor cell culture was established, and its conditioned medium was developed for anti-aging therapy. EPC-CM improved signs of skin aging in clinical study, possibly via activation of cellular the defense system, as supported by in vitro results.

Project description:BackgroundActivin A is a protein that participates principally in reproductive functions. In the adult brain, Activin is neuroprotective, but its role in brain development is still elusive.Methodology/principal findingsWe studied if Activin A influences proliferation, differentiation or survival in rat cerebrocortical neural progenitor cells (NPC). After stimulation of NPC with Activin A, phosphorylation and nuclear translocation of Smad 2/3 were induced. In proliferating NPC, Activin produced a significant decrease in cell area and also a discrete increase in the number of neurons in the presence of the mitogen Fibroblast Growth Factor 2. The percentages of cells incorporating BrdU, or positive for the undifferentiated NPC markers Nestin and Sox2, were unchanged after incubation with Activin. In differentiating conditions, continuous treatment with Activin A significantly increased the number of neurons without affecting astroglial differentiation or causing apoptotic death. In cells cultured by extended periods, Activin treatment produced further increases in the proportion of neurons, excluding premature cell cycle exit. In clonal assays, Activin significantly increased neuronal numbers per colony, supporting an instructive role. Activin-induced neurogenesis was dependent on activation of its receptors, since incubation with the type I receptor inhibitor SB431542 or the ligand-trap Follistatin prevented neuronal differentiation. Interestingly, SB431542 or Follistatin by themselves abolished neurogenesis and increased astrogliogenesis, to a similar extent to that induced by Bone Morphogenetic Protein (BMP)4. Co-incubation of these Activin inhibitors with the BMP antagonist Dorsomorphin restored neuronal and astrocytic differentiation to control levels.ConclusionsOur results show an instructive neuronal effect of Activin A in cortical NPC in vitro, pointing out to a relevant role of this cytokine in the specification of NPC towards a neuronal phenotype.

Project description:Myeloid angiogenic cells (MAC) derive from hematopoietic stem/progenitor cells (HSPCs) that are mobilized from the bone marrow. They home to sites of neovascularization and contribute to angiogenesis by production of paracrine factors. The number and function of proangiogenic cells are impaired in patients with diabetes or cardiovascular diseases. Both conditions can be accompanied by decreased levels of heme oxygenase-1 (HMOX1), cytoprotective, heme-degrading enzyme. Our study is aimed at investigating whether precursors of myeloid angiogenic cells (PACs) treated with known pharmaceuticals would produce media with better proangiogenic activity in vitro and if such media can be used to stimulate blood vessel growth in vivo. We used G-CSF-mobilized CD34+ HSPCs, FACS-sorted from healthy donor peripheral blood mononuclear cells (PBMCs). Sorted cells were predominantly CD133+. CD34+ cells after six days in culture were stimulated with atorvastatin (AT), acetylsalicylic acid (ASA), sulforaphane (SR), resveratrol (RV), or metformin (Met) for 48 h. Conditioned media from such cells were then used to stimulate human aortic endothelial cells (HAoECs) to enhance tube-like structure formation in a Matrigel assay. The only stimulant that enhanced PAC paracrine angiogenic activity was atorvastatin, which also had ability to stabilize endothelial tubes in vitro. On the other hand, the only one that induced heme oxygenase-1 expression was sulforaphane, a known activator of a HMOX1 inducer-NRF2. None of the stimulants changed significantly the levels of 30 cytokines and growth factors tested with the multiplex test. Then, we used atorvastatin-stimulated cells or conditioned media from them in the Matrigel plug in vivo angiogenic assay. Neither AT alone in control media nor conditioned media nor AT-stimulated cells affected numbers of endothelial cells in the plug or plug's vascularization. Concluding, high concentrations of atorvastatin stabilize tubes and enhance the paracrine angiogenic activity of human PAC cells in vitro. However, the effect was not observed in vivo. Therefore, the use of conditioned media from atorvastatin-treated PAC is not a promising therapeutic strategy to enhance angiogenesis.

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Conditioned media from AICAR-treated skeletal muscle cells increases neuronal differentiation of adult neural progenitor cells.

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Conditioned media from AICAR-treated skeletal muscle cells increases neuronal differentiation of adult neural progenitor cells.

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