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Contingent intramuscular boosting of P2XR7 axis improves motor function in transgenic ALS mice.
- Source :
-
Cellular and molecular life sciences : CMLS [Cell Mol Life Sci] 2021 Dec 22; Vol. 79 (1), pp. 7. Date of Electronic Publication: 2021 Dec 22. - Publication Year :
- 2021
-
Abstract
- Amyotrophic lateral sclerosis is a fatal neurodegenerative disorder that leads to progressive degeneration of motor neurons and severe muscle atrophy without effective treatment. Most research on the disease has been focused on studying motor neurons and supporting cells of the central nervous system. Strikingly, the recent observations have suggested that morpho-functional alterations in skeletal muscle precede motor neuron degeneration, bolstering the interest in studying muscle tissue as a potential target for the delivery of therapies. We previously showed that the systemic administration of the P2XR7 agonist, 2'(3')-O-(4-benzoylbenzoyl) adenosine 5-triphosphate (BzATP), enhanced the metabolism and promoted the myogenesis of new fibres in the skeletal muscles of SOD1G93A mice. Here we further corroborated this evidence showing that intramuscular administration of BzATP improved the motor performance of ALS mice by enhancing satellite cells and the muscle pro-regenerative activity of infiltrating macrophages. The preservation of the skeletal muscle retrogradely propagated along with the motor unit, suggesting that backward signalling from the muscle could impinge on motor neuron death. In addition to providing the basis for a suitable adjunct multisystem therapeutic approach in ALS, these data point out that the muscle should be at the centre of ALS research as a target tissue to address novel therapies in combination with those oriented to the CNS.<br /> (© 2021. The Author(s).)
- Subjects :
- Adenosine Triphosphate administration & dosage
Adenosine Triphosphate analogs & derivatives
Adenosine Triphosphate pharmacology
Animals
Axons pathology
Biomarkers metabolism
Cell Differentiation drug effects
Cell Polarity drug effects
Cell Proliferation drug effects
Cell Survival drug effects
Denervation
Disease Models, Animal
Disease Progression
Female
Hindlimb pathology
Humans
Inflammation pathology
Injections, Intramuscular
MAP Kinase Signaling System drug effects
Macrophages drug effects
Macrophages metabolism
Male
Mice, Transgenic
Motor Neurons drug effects
Motor Neurons pathology
Muscle, Skeletal drug effects
Muscle, Skeletal innervation
Muscular Atrophy pathology
Phenotype
Satellite Cells, Skeletal Muscle drug effects
Satellite Cells, Skeletal Muscle pathology
Schwann Cells pathology
Sciatic Nerve drug effects
Sciatic Nerve pathology
Amyotrophic Lateral Sclerosis metabolism
Amyotrophic Lateral Sclerosis physiopathology
Motor Activity physiology
Muscle, Skeletal metabolism
Muscle, Skeletal physiopathology
Receptors, Purinergic P2X7 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1420-9071
- Volume :
- 79
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Cellular and molecular life sciences : CMLS
- Publication Type :
- Academic Journal
- Accession number :
- 34936028
- Full Text :
- https://doi.org/10.1007/s00018-021-04070-8