Amyotrophic Lateral Sclerosis (ALS) is the most common disease involving motor neurons that occurs in both sporadic (sSLA) and familial (fSLA) forms. While the phenotype of fSLA and sSLA is similar, the molecular mechanisms underlying the defects of neuromuscular junctions (NMJ) observed in ALS are still not known but these defects suggest an altered plasticity of the junction itself. It has been demonstrated that fibers with different physiological properties (slow, fast-fatigue resistant, fast-fatiguable) are differently susceptible to ALS-induced damages and denervation, soleus (slow fibers muscle) is resistant and plastic, while gastrocnemius (fast twitch and fast fatigable muscle) is extremely sensitive to the denervation. Diaphragm is a peculiar muscle in which a blend of slow and fast twitch fibers is present and this composition led to an intermediate response to the pathology-induced denervation. Neuromuscular junction destruction and disassembly is one of the first hallmarks of ALS, a progressive neurodegenerative disorder characterized by the selective loss of motoneurons in the spinal cord, brain stem and motor cortex. Here we analyzed the fine structure of the neuromuscular junctions of diaphragm in SOD1G93A mice at the onset of the disease, and found that the diaphragm is already significantly denervated in early symptomatic stages of the disease (P85-P95). The remaining presynaptic terminals showed a general reduction in the size of the synaptic vesicle pool and approximately a 40% of presynaptic profiles contained altered mitochondria. Continuous administration of the anabolic steroid nandrolone from a presymptomatic stage of the disease, preserved the muscle mass in mutant mice and increased the synaptic activity both in terms of reduction in the number of docked and recycling vesicles and in terms of increased area of acetylcholine receptor clusters. These effects were accompanied by an almost complete reduction of altered mitochondria in presynaptic terminals. However, innervation of muscle fibers was only slightly increased, suggesting that nandrolone itself or muscle positive signals that prevent morphological alteration in mitochondria and stimulate presynaptic activity are not sufficient to efficiently prevent denervation.
Characterztion of the neuromuscular junctions in a mouse model of ALS: effect of early administration of Nandrolone / V. Cappello, E. Vezzoli, M. Righi, M. Bentivoglio, G. Pietrini, M. Francolini. ((Intervento presentato al 10. convegno MCM 2011 tenutosi a Urbino nel 2011.
|Titolo:||Characterztion of the neuromuscular junctions in a mouse model of ALS: effect of early administration of Nandrolone|
|Data di pubblicazione:||2011|
|Parole Chiave:||ALS ; SOD1G93A mice ; neuromuscular junction ; diaphragm ; nandrolone|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Enti collegati al convegno:||Italian Society of Microscopical Science|
Austrian Society for Electron Microscopy
Croatian Microscopy Society
Czechoslovakian Microscopy Society
Hungarian Society of Microscopical Science
Serbian Society for Microscopy
Slovene Society for Microscopy
|Citazione:||Characterztion of the neuromuscular junctions in a mouse model of ALS: effect of early administration of Nandrolone / V. Cappello, E. Vezzoli, M. Righi, M. Bentivoglio, G. Pietrini, M. Francolini. ((Intervento presentato al 10. convegno MCM 2011 tenutosi a Urbino nel 2011.|
|Appare nelle tipologie:||14 - Intervento a convegno non pubblicato|