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Neuro‐Cells therapy improves motor outcomes and suppresses inflammation during experimental syndrome of amyotrophic lateral sclerosis in mice

AIMS: Mutations in DNA/RNA‐binding factor (fused‐in‐sarcoma) FUS and superoxide dismutase‐1 (SOD‐1) cause amyotrophic lateral sclerosis (ALS). They were reproduced in SOD‐1‐G93A (SOD‐1) and new FUS[1‐359]‐transgenic (FUS‐tg) mice, where inflammation contributes to disease progression. The effects of...

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Autores principales: de Munter, Johannes P.J.M., Shafarevich, Igor, Liundup, Alexei, Pavlov, Dmitrii, Wolters, Erik Ch, Gorlova, Anna, Veniaminova, Ekaterina, Umriukhin, Aleksei, Kalueff, Allan, Svistunov, Andrei, Kramer, Boris W., Lesch, Klaus‐Peter, Strekalova, Tatyana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7163689/
https://www.ncbi.nlm.nih.gov/pubmed/31867846
http://dx.doi.org/10.1111/cns.13280
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author de Munter, Johannes P.J.M.
Shafarevich, Igor
Liundup, Alexei
Pavlov, Dmitrii
Wolters, Erik Ch
Gorlova, Anna
Veniaminova, Ekaterina
Umriukhin, Aleksei
Kalueff, Allan
Svistunov, Andrei
Kramer, Boris W.
Lesch, Klaus‐Peter
Strekalova, Tatyana
author_facet de Munter, Johannes P.J.M.
Shafarevich, Igor
Liundup, Alexei
Pavlov, Dmitrii
Wolters, Erik Ch
Gorlova, Anna
Veniaminova, Ekaterina
Umriukhin, Aleksei
Kalueff, Allan
Svistunov, Andrei
Kramer, Boris W.
Lesch, Klaus‐Peter
Strekalova, Tatyana
author_sort de Munter, Johannes P.J.M.
collection PubMed
description AIMS: Mutations in DNA/RNA‐binding factor (fused‐in‐sarcoma) FUS and superoxide dismutase‐1 (SOD‐1) cause amyotrophic lateral sclerosis (ALS). They were reproduced in SOD‐1‐G93A (SOD‐1) and new FUS[1‐359]‐transgenic (FUS‐tg) mice, where inflammation contributes to disease progression. The effects of standard disease therapy and anti‐inflammatory treatments were investigated using these mutants. METHODS: FUS‐tg mice or controls received either vehicle, or standard ALS treatment riluzole (8 mg/kg/day), or anti‐inflammatory drug a selective blocker of cyclooxygenase‐2 celecoxib (30 mg/kg/day) for six weeks, or a single intracerebroventricular (i.c.v.) infusion of Neuro‐Cells (a preparation of 1.39 × 10(6) mesenchymal and hemopoietic human stem cells, containing 5 × 10(5) of CD34(+) cells), which showed anti‐inflammatory properties. SOD‐1 mice received i.c.v.‐administration of Neuro‐Cells or vehicle. RESULTS: All FUS‐tg‐treated animals displayed less marked reductions in weight gain, food/water intake, and motor deficits than FUS‐tg‐vehicle‐treated mice. Neuro‐Cell‐treated mutants had reduced muscle atrophy and lumbar motor neuron degeneration. This group but not celecoxib‐FUS‐tg‐treated mice had ameliorated motor performance and lumbar expression of microglial activation marker, ionized calcium‐binding adapter molecule‐1 (Iba‐1), and glycogen‐synthase‐kinase‐3ß (GSK‐3ß). The Neuro‐Cells‐treated‐SOD‐1 mice showed better motor functions than vehicle‐treated‐SOD‐1 group. CONCLUSION: The neuropathology in FUS‐tg mice is sensitive to standard ALS treatments and Neuro‐Cells infusion. The latter improves motor outcomes in two ALS models possibly by suppressing microglial activation.
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spelling pubmed-71636892020-04-20 Neuro‐Cells therapy improves motor outcomes and suppresses inflammation during experimental syndrome of amyotrophic lateral sclerosis in mice de Munter, Johannes P.J.M. Shafarevich, Igor Liundup, Alexei Pavlov, Dmitrii Wolters, Erik Ch Gorlova, Anna Veniaminova, Ekaterina Umriukhin, Aleksei Kalueff, Allan Svistunov, Andrei Kramer, Boris W. Lesch, Klaus‐Peter Strekalova, Tatyana CNS Neurosci Ther Original Articles AIMS: Mutations in DNA/RNA‐binding factor (fused‐in‐sarcoma) FUS and superoxide dismutase‐1 (SOD‐1) cause amyotrophic lateral sclerosis (ALS). They were reproduced in SOD‐1‐G93A (SOD‐1) and new FUS[1‐359]‐transgenic (FUS‐tg) mice, where inflammation contributes to disease progression. The effects of standard disease therapy and anti‐inflammatory treatments were investigated using these mutants. METHODS: FUS‐tg mice or controls received either vehicle, or standard ALS treatment riluzole (8 mg/kg/day), or anti‐inflammatory drug a selective blocker of cyclooxygenase‐2 celecoxib (30 mg/kg/day) for six weeks, or a single intracerebroventricular (i.c.v.) infusion of Neuro‐Cells (a preparation of 1.39 × 10(6) mesenchymal and hemopoietic human stem cells, containing 5 × 10(5) of CD34(+) cells), which showed anti‐inflammatory properties. SOD‐1 mice received i.c.v.‐administration of Neuro‐Cells or vehicle. RESULTS: All FUS‐tg‐treated animals displayed less marked reductions in weight gain, food/water intake, and motor deficits than FUS‐tg‐vehicle‐treated mice. Neuro‐Cell‐treated mutants had reduced muscle atrophy and lumbar motor neuron degeneration. This group but not celecoxib‐FUS‐tg‐treated mice had ameliorated motor performance and lumbar expression of microglial activation marker, ionized calcium‐binding adapter molecule‐1 (Iba‐1), and glycogen‐synthase‐kinase‐3ß (GSK‐3ß). The Neuro‐Cells‐treated‐SOD‐1 mice showed better motor functions than vehicle‐treated‐SOD‐1 group. CONCLUSION: The neuropathology in FUS‐tg mice is sensitive to standard ALS treatments and Neuro‐Cells infusion. The latter improves motor outcomes in two ALS models possibly by suppressing microglial activation. John Wiley and Sons Inc. 2019-12-23 /pmc/articles/PMC7163689/ /pubmed/31867846 http://dx.doi.org/10.1111/cns.13280 Text en © 2019 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
de Munter, Johannes P.J.M.
Shafarevich, Igor
Liundup, Alexei
Pavlov, Dmitrii
Wolters, Erik Ch
Gorlova, Anna
Veniaminova, Ekaterina
Umriukhin, Aleksei
Kalueff, Allan
Svistunov, Andrei
Kramer, Boris W.
Lesch, Klaus‐Peter
Strekalova, Tatyana
Neuro‐Cells therapy improves motor outcomes and suppresses inflammation during experimental syndrome of amyotrophic lateral sclerosis in mice
title Neuro‐Cells therapy improves motor outcomes and suppresses inflammation during experimental syndrome of amyotrophic lateral sclerosis in mice
title_full Neuro‐Cells therapy improves motor outcomes and suppresses inflammation during experimental syndrome of amyotrophic lateral sclerosis in mice
title_fullStr Neuro‐Cells therapy improves motor outcomes and suppresses inflammation during experimental syndrome of amyotrophic lateral sclerosis in mice
title_full_unstemmed Neuro‐Cells therapy improves motor outcomes and suppresses inflammation during experimental syndrome of amyotrophic lateral sclerosis in mice
title_short Neuro‐Cells therapy improves motor outcomes and suppresses inflammation during experimental syndrome of amyotrophic lateral sclerosis in mice
title_sort neuro‐cells therapy improves motor outcomes and suppresses inflammation during experimental syndrome of amyotrophic lateral sclerosis in mice
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7163689/
https://www.ncbi.nlm.nih.gov/pubmed/31867846
http://dx.doi.org/10.1111/cns.13280
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