Research output: Contribution to journal › Article › peer-review
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.
In: CNS Neuroscience and Therapeutics, Vol. 26, No. 5, 05.2020, p. 504-517.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Neuro-Cells therapy improves motor outcomes and suppresses inflammation during experimental syndrome of amyotrophic lateral sclerosis in mice
AU - de Munter, Johannes P.J.M.
AU - Shafarevich, Igor
AU - Liundup, Alexei
AU - Pavlov, Dmitrii
AU - Wolters, Erik Ch
AU - Gorlova, Anna
AU - Veniaminova, Ekaterina
AU - Umriukhin, Aleksei
AU - Kalueff, Allan
AU - Svistunov, Andrei
AU - Kramer, Boris W.
AU - Lesch, Klaus Peter
AU - Strekalova, Tatyana
PY - 2020/5
Y1 - 2020/5
N2 - 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.
AB - 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.
KW - amyotrophic lateral sclerosis (ALS)
KW - fused in sarcoma (FUS) protein
KW - glycogen-synthase kinase-3ß (GSK-3ß)
KW - microglia activation
KW - mouse
KW - stem cell therapy
KW - superoxide dismutase-1 (SOD-1) G93A mice
UR - http://www.scopus.com/inward/record.url?scp=85076897663&partnerID=8YFLogxK
U2 - 10.1111/cns.13280
DO - 10.1111/cns.13280
M3 - Article
AN - SCOPUS:85076897663
VL - 26
SP - 504
EP - 517
JO - CNS Neuroscience and Therapeutics
JF - CNS Neuroscience and Therapeutics
SN - 1755-5930
IS - 5
ER -
ID: 51802871