title: Expression of Muscle-Specific MiRNA 206 in the Progression of Disease in a Murine SMA Model.
abstract: Spinal muscular atrophy (SMA) is a severe neuromuscular disease, the most common in infancy, and the third one among young people under 18 years. The major pathological landmark of SMA is a selective degeneration of lower motor neurons, resulting in progressive skeletal muscle denervation, atrophy, and paralysis. Recently, it has been shown that specific or general changes in the activity of ribonucleoprotein containing micro RNAs (miRNAs) play a role in the development of SMA. Additionally miRNA-206 has been shown to be required for efficient regeneration of neuromuscular synapses after acute nerve injury in an ALS mouse model. Therefore, we correlated the morphology and the architecture of the neuromuscular junctions (NMJs) of quadriceps, a muscle affected in the early stage of the disease, with the expression levels of miRNA-206 in a mouse model of intermediate SMA (SMAII), one of the most frequently used experimental model. Our results showed a decrease in the percentage of type II fibers, an increase in atrophic muscle fibers and a remarkable accumulation of neurofilament (NF) in the pre-synaptic terminal of the NMJs in the quadriceps of SMAII mice. Furthermore, molecular investigation showed a direct link between miRNA-206-HDAC4-FGFBP1, and in particular, a strong up-regulation of this pathway in the late phase of the disease. We propose that miRNA-206 is activated as survival endogenous mechanism, although not sufficient to rescue the integrity of motor neurons. We speculate that early modulation of miRNA-206 expression might delay SMA neurodegenerative pathway and that miRNA-206 could be an innovative, still relatively unexplored, therapeutic target for SMA.
authors.affiliation: Neuroscience Institute Cavalieri Ottolenghi, Department of Neuroscience, University of Turin, Turin, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Valsecchi
authors.affiliation: Neuroscience Institute Cavalieri Ottolenghi, Department of Neuroscience, University of Turin, Turin, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Boido
authors.affiliation: Neuroscience Institute Cavalieri Ottolenghi, Department of Neuroscience, University of Turin, Turin, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: De Amicis
authors.affiliation: Neuroscience Institute Cavalieri Ottolenghi, Department of Neuroscience, University of Turin, Turin, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Piras
authors.affiliation: Neuroscience Institute Cavalieri Ottolenghi, Department of Neuroscience, University of Turin, Turin, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Vercelli
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009046:Motor Neurons / Q000378:metabolism* / Q000473:pathology; D009134:Muscular Atrophy, Spinal / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D002352:Carrier Proteins; C489453:Fgfbp1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D035683:MicroRNAs; C540669:Mirn206 microRNA, mouse; C498618:Hdac5 protein, mouse; D006655:Histone Deacetylases