| Increased levels of p70S6 phosphorylation in the G93A mouse model of Amyotrophic Lateral Sclerosis and in valine-exposed cortical neurons in culture. | |
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MedLine Citation:
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PMID: 20832409 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The higher risk factor for Amyotrophic Lateral Sclerosis (ALS) among Italian soccer players is a question that is still debated. One of the hypotheses that have been formulated to explain a possible link between ALS and soccer players is related to the abuse of dietary supplements and drugs for enhancing sporting performance. In particular, it has been reported that branched-chain amino acids (BCAAs) are widely used among athletes as nutritional supplements. To observe the possible effect of BCAAs on neuronal electrical properties, we performed electrophysiological experiments on Control cultured cortical neurons and on neurons after BCAA treatment. BCAA-treated neurons showed hyperexcitability and rapamycin was able to suppress it and significantly reduce the level of mTOR, Akt and p70S6 phosphorylation. Interestingly, the hyperexcitability previously reported in cortical neurons from a genetic mouse model of ALS (G93A) was also reversed by rapamycin treatment. Moreover, both G93A and valine-treated neurons presented significantly higher levels of Pp70S6 when compared to control neurons, strongly indicating the involvement of this substrate in ALS pathology. Finally, we performed electrophysiological experiments on motor cortex slices from Control and G93A mice and those fed with a BCAA-enriched diet. We observed that neuron excitability was comparable between G93A and BCAA-enriched diet mice, but was significantly higher than in Control mice. These findings, besides strongly indicating that BCAAs specifically induce hyperexcitability, seem to suggest the involvement of p70S6 substrate in ALS pathology. |
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Authors:
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Irene Carunchio; Livia Curcio; Massimo Pieri; Francesca Pica; Silvia Caioli; Maria Teresa Viscomi; Marco Molinari; Nadia Canu; Giorgio Bernardi; Cristina Zona |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-09-09 |
Journal Detail:
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Title: Experimental neurology Volume: 226 ISSN: 1090-2430 ISO Abbreviation: Exp. Neurol. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-10-15 Completed Date: 2010-10-28 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0370712 Medline TA: Exp Neurol Country: United States |
Other Details:
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Languages: eng Pagination: 218-30 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Neuroscience, University of Rome Tor Vergata, Via Montpellier, 1, 00133, Rome, Italy. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Action Potentials
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drug effects Amino Acids, Branched-Chain / metabolism Amyotrophic Lateral Sclerosis / genetics, metabolism*, pathology Animals Blotting, Western Cell Survival / drug effects Cells, Cultured Cerebral Cortex / cytology, drug effects, metabolism* Dose-Response Relationship, Drug Electrophysiology Humans Immunosuppressive Agents / pharmacology Intracellular Signaling Peptides and Proteins / metabolism Mice Mice, Transgenic Neurons / drug effects, metabolism* Phosphorylation Protein-Serine-Threonine Kinases / metabolism Sirolimus / pharmacology Sodium Channels / drug effects Superoxide Dismutase / genetics Valine / pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/Amino Acids, Branched-Chain; 0/Immunosuppressive Agents; 0/Intracellular Signaling Peptides and Proteins; 0/Sodium Channels; 53123-88-9/Sirolimus; 7004-03-7/Valine; EC 1.15.1.-/superoxide dismutase 1; EC 1.15.1.1/Superoxide Dismutase; EC 2.7.1.-/mTOR protein; EC 2.7.11.1/Protein-Serine-Threonine Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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