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

Johannes P. J. M. de Munter, Igor Shafarevich, Alexei Liundup, Dmitrii Pavlov, Erik Ch Wolters, Anna Gorlova, Ekaterina Veniaminova, Aleksei Umriukhin, Allan Kalueff, Andrei Svistunov, Boris W. Kramer*, Klaus-Peter Lesch, Tatyana Strekalova*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

16 Citations (Web of Science)

Abstract

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 x 10(6) mesenchymal and hemopoietic human stem cells, containing 5 x 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-3 ss (GSK-3 ss). 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.

Original languageEnglish
Pages (from-to)504-517
Number of pages14
JournalCNS Neuroscience & Therapeutics
Volume26
Issue number5
Early online date23 Dec 2019
DOIs
Publication statusPublished - May 2020

Keywords

  • amyotrophic lateral sclerosis (ALS)
  • fused in sarcoma (FUS) protein
  • glycogen-synthase kinase-3 ss (GSK-3 ss)
  • microglia activation
  • mouse
  • stem cell therapy
  • superoxide dismutase-1 (SOD-1) G93A mice
  • MESENCHYMAL STEM-CELLS
  • MARROW STROMAL CELLS
  • INJURED SPINAL-CORD
  • MOUSE MODEL
  • TRANSPLANTATION
  • MUTATIONS
  • PHENOTYPE
  • STRESS
  • TRIAL

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