Neuro-Cells therapy improves motor outcomes and suppresses inflammation during experimental syndrome of amyotrophic lateral sclerosis in mice
| Autor: | Klaus-Peter Lesch, Boris W. Kramer, Ekaterina Veniaminova, Anna Gorlova, Andrei Svistunov, Tatyana Strekalova, D. A. Pavlov, Alexei Liundup, Igor Shafarevich, Erik Ch. Wolters, Aleksei Umriukhin, Allan V. Kalueff, Johannes P.J.M. de Munter |
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| Přispěvatelé: | Psychiatrie & Neuropsychologie, RS: MHeNs - R3 - Neuroscience, Promovendi MHN, Kindergeneeskunde, MUMC+: MA Medische Staf Kindergeneeskunde (9) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
medicine.medical_treatment MOUSE PHENOTYPE ANIMAL EXPERIMENT stem cell therapy INJURED SPINAL-CORD Mice 0302 clinical medicine HUMAN CELL Pharmacology (medical) CELECOXIB Cells Cultured Motor Neurons FUSED IN SARCOMA (FUS) PROTEIN fused in sarcoma (FUS) protein MARROW STROMAL CELLS FLUID INTAKE TRANSGENIC MOUSE Hematopoietic Stem Cell Transplantation HUMAN SUPEROXIDE DISMUTASE-1 (SOD-1) G93A MICE Stem-cell therapy MOUSE MODEL Riluzole Motor Skills Disorders Psychiatry and Mental health EXPERIMENTAL NEUROLOGIC DISEASE Editorial IONIZED CALCIUM BINDING ADAPTER MOLECULE 1 TRIAL BODY WEIGHT GAIN DRUG EFFECT medicine.medical_specialty microglia activation COPPER ZINC SUPEROXIDE DISMUTASE 03 medical and health sciences DISEASE EXACERBATION NERVE CELL DEGENERATION Physiology (medical) NONHUMAN mouse Pharmacology MUTATIONS Amyotrophic Lateral Sclerosis medicine.disease 030104 developmental biology Endocrinology PILOT STUDY 030217 neurology & neurosurgery 0301 basic medicine amyotrophic lateral sclerosis (ALS) STRESS HEMATOPOIETIC STEM CELL Anti-Inflammatory Agents ANIMAL MODEL UNCLASSIFIED DRUG glycogen-synthase kinase-3 ss (GSK-3 ss) GLYCOGEN-SYNTHASE KINASE-3ß (GSK-3ß) Amyotrophic lateral sclerosis MSOD1 MOUSE CELL MARKER MOTOR PERFORMANCE STEM CELL TRANSPLANTATION Muscle atrophy MICROGLIA ACTIVATION Treatment Outcome superoxide dismutase-1 (SOD-1) G93A mice AMYOTROPHIC LATERAL SCLEROSIS (ALS) GLYCOGEN SYNTHASE KINASE 3BETA AMYOTROPHIC LATERAL SCLEROSIS Inflammation Mediators Stem cell medicine.symptom medicine.drug STEM CELL THERAPY Mice Transgenic Inflammation MESENCHYMAL STEM CELL MESENCHYMAL STEM-CELLS INFLAMMATION ANIMAL TISSUE Internal medicine GENE MUTATION medicine Animals ARTICLE MUSCLE ATROPHY Injections Intraventricular MALE Superoxide Dismutase business.industry TRANSPLANTATION CONTROLLED STUDY Transplantation RILUZOLE Celecoxib business |
| Zdroj: | CNS Neuroscience & Therapeutics, 26(5), 504-517. Wiley CNS Neuroscience & Therapeutics CNS Neuroscience and Therapeutics |
| ISSN: | 1755-5949 1755-5930 |
| Popis: | 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 × 106 mesenchymal and hemopoietic human stem cells, containing 5 × 105 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. © 2019 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd We thank ?5-100? Russian Excellence Program, Prof. Daniel C. Anthony, Diana Babayevskaya, and Arina Kosakova for their highly valuable contribution. ?Neuro-Cells? preparation was provided by Neuroplast BV, Maastricht, Netherlands. |
| Databáze: | OpenAIRE |
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