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Muscle Expression of SOD1(G93A) Modulates microRNA and mRNA Transcription Pattern Associated with the Myelination Process in the Spinal Cord of Transgenic Mice.

Dobrowolny G, Bernardini C, Martini M, Baranzini M, Barba M, Musarò A - Front Cell Neurosci (2015)

Bottom Line: A crucial system severely affected in several neuromuscular diseases is the loss of effective connection between muscle and nerve, leading to a pathological non-communication between the two tissues.Increasing evidences suggest that damage to motor neurons is enhanced by alterations in the neighboring non-neuronal cells and indicate that altered skeletal muscle might be the source of signals that impinge motor neuron activity and survival.Our study provides insights into the pathophysiological interplay between muscle and nerve and supports the hypothesis that muscle is a source of signals that can either positively or negatively affect the nervous system.

View Article: PubMed Central - PubMed

Affiliation: DAHFMO-Unit of Histology and Medical Embryology, Institute Pasteur-Cenci Bolognetti, IIM, Sapienza University of Rome Rome, Italy ; Center for Life Nano Science at Sapienza, Istituto Italiano di Tecnologia Rome, Italy.

ABSTRACT
A crucial system severely affected in several neuromuscular diseases is the loss of effective connection between muscle and nerve, leading to a pathological non-communication between the two tissues. One of the best examples of impaired interplay between muscle and nerve is Amyotrophic Lateral Sclerosis, a neurodegenerative disease characterized by degeneration of motor neurons and muscle atrophy. Increasing evidences suggest that damage to motor neurons is enhanced by alterations in the neighboring non-neuronal cells and indicate that altered skeletal muscle might be the source of signals that impinge motor neuron activity and survival. Here we investigated whether muscle selective expression of SOD1(G93A) mutant gene modulates mRNAs and miRNAs expression at the level of spinal cord of MLC/SOD1(G93A) mice. Using a Taqman array, the Affymetrix Mouse Gene 2.0 ST approach and the MiRwalk 2.0 database, which provides information on miRNA and their predicted target genes, we revealed that muscle specific expression of SOD1(G93A) modulates relevant molecules of the genetic and epigenetic circuitry of myelin homeostasis in spinal cord of transgenic mice. Our study provides insights into the pathophysiological interplay between muscle and nerve and supports the hypothesis that muscle is a source of signals that can either positively or negatively affect the nervous system.

No MeSH data available.


Related in: MedlinePlus

Hypomyelination in the sciatic nerve of MLC/SOD1G93A mice. (A) Photographs showing the mouse sciatic nerve strained with toluidine blue. White arrowhead indicates onion bulb structure (40X magnification) Scale bar = 20 μm. (B) The average g-ratios. (C) The average g-ratio for each axonal diameter (1–3, 3–5, 5–7, >7 μm). Values are expressed as mean ± SEM fibers. *p < 0.05; ****p < 0.0001 compared to wild type (Wt).
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Figure 5: Hypomyelination in the sciatic nerve of MLC/SOD1G93A mice. (A) Photographs showing the mouse sciatic nerve strained with toluidine blue. White arrowhead indicates onion bulb structure (40X magnification) Scale bar = 20 μm. (B) The average g-ratios. (C) The average g-ratio for each axonal diameter (1–3, 3–5, 5–7, >7 μm). Values are expressed as mean ± SEM fibers. *p < 0.05; ****p < 0.0001 compared to wild type (Wt).

Mentions: Different reports indicate that ALS might be associated with motor nerve fiber (Echaniz-Laguna et al., 2006; Rajabally and Jacob, 2008; Ahdab et al., 2013). Previously, we demonstrated that the peripheral nerve was severely compromised in the global SOD1G93A mutant mice, which displayed loss of Schmidt-Lantermann incisures, a disproportionately thick myelin sheath, abundant double onion bulb structures, and increased demyelinated axons (Dobrowolny et al., 2008a). To assess whether muscle specific expression of SOD1 mutant gene induces a peripheral alteration of axon myelination we calculated the ratio of axon diameter to total fiber diameter (g-ratio) (Michailov et al., 2004). The Figure 5A shows the cross-sections of wild type and MLC/SOD1G93A sciatic nerves stained with toluidine blue. The histological analysis of the peripheral nerve of the MLC/SOD1G93A displayed the presence of double onion bulb structures. Moreover, the g-ratio in the transgenic sciatic nerves was significantly increased (Figure 5B) independently of the axonal diameter (Figure 5C), indicating that muscle specific expression of SOD1 mutant gene induces hypomyelination in the sciatic nerve of transgenic mice.


Muscle Expression of SOD1(G93A) Modulates microRNA and mRNA Transcription Pattern Associated with the Myelination Process in the Spinal Cord of Transgenic Mice.

Dobrowolny G, Bernardini C, Martini M, Baranzini M, Barba M, Musarò A - Front Cell Neurosci (2015)

Hypomyelination in the sciatic nerve of MLC/SOD1G93A mice. (A) Photographs showing the mouse sciatic nerve strained with toluidine blue. White arrowhead indicates onion bulb structure (40X magnification) Scale bar = 20 μm. (B) The average g-ratios. (C) The average g-ratio for each axonal diameter (1–3, 3–5, 5–7, >7 μm). Values are expressed as mean ± SEM fibers. *p < 0.05; ****p < 0.0001 compared to wild type (Wt).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4664730&req=5

Figure 5: Hypomyelination in the sciatic nerve of MLC/SOD1G93A mice. (A) Photographs showing the mouse sciatic nerve strained with toluidine blue. White arrowhead indicates onion bulb structure (40X magnification) Scale bar = 20 μm. (B) The average g-ratios. (C) The average g-ratio for each axonal diameter (1–3, 3–5, 5–7, >7 μm). Values are expressed as mean ± SEM fibers. *p < 0.05; ****p < 0.0001 compared to wild type (Wt).
Mentions: Different reports indicate that ALS might be associated with motor nerve fiber (Echaniz-Laguna et al., 2006; Rajabally and Jacob, 2008; Ahdab et al., 2013). Previously, we demonstrated that the peripheral nerve was severely compromised in the global SOD1G93A mutant mice, which displayed loss of Schmidt-Lantermann incisures, a disproportionately thick myelin sheath, abundant double onion bulb structures, and increased demyelinated axons (Dobrowolny et al., 2008a). To assess whether muscle specific expression of SOD1 mutant gene induces a peripheral alteration of axon myelination we calculated the ratio of axon diameter to total fiber diameter (g-ratio) (Michailov et al., 2004). The Figure 5A shows the cross-sections of wild type and MLC/SOD1G93A sciatic nerves stained with toluidine blue. The histological analysis of the peripheral nerve of the MLC/SOD1G93A displayed the presence of double onion bulb structures. Moreover, the g-ratio in the transgenic sciatic nerves was significantly increased (Figure 5B) independently of the axonal diameter (Figure 5C), indicating that muscle specific expression of SOD1 mutant gene induces hypomyelination in the sciatic nerve of transgenic mice.

Bottom Line: A crucial system severely affected in several neuromuscular diseases is the loss of effective connection between muscle and nerve, leading to a pathological non-communication between the two tissues.Increasing evidences suggest that damage to motor neurons is enhanced by alterations in the neighboring non-neuronal cells and indicate that altered skeletal muscle might be the source of signals that impinge motor neuron activity and survival.Our study provides insights into the pathophysiological interplay between muscle and nerve and supports the hypothesis that muscle is a source of signals that can either positively or negatively affect the nervous system.

View Article: PubMed Central - PubMed

Affiliation: DAHFMO-Unit of Histology and Medical Embryology, Institute Pasteur-Cenci Bolognetti, IIM, Sapienza University of Rome Rome, Italy ; Center for Life Nano Science at Sapienza, Istituto Italiano di Tecnologia Rome, Italy.

ABSTRACT
A crucial system severely affected in several neuromuscular diseases is the loss of effective connection between muscle and nerve, leading to a pathological non-communication between the two tissues. One of the best examples of impaired interplay between muscle and nerve is Amyotrophic Lateral Sclerosis, a neurodegenerative disease characterized by degeneration of motor neurons and muscle atrophy. Increasing evidences suggest that damage to motor neurons is enhanced by alterations in the neighboring non-neuronal cells and indicate that altered skeletal muscle might be the source of signals that impinge motor neuron activity and survival. Here we investigated whether muscle selective expression of SOD1(G93A) mutant gene modulates mRNAs and miRNAs expression at the level of spinal cord of MLC/SOD1(G93A) mice. Using a Taqman array, the Affymetrix Mouse Gene 2.0 ST approach and the MiRwalk 2.0 database, which provides information on miRNA and their predicted target genes, we revealed that muscle specific expression of SOD1(G93A) modulates relevant molecules of the genetic and epigenetic circuitry of myelin homeostasis in spinal cord of transgenic mice. Our study provides insights into the pathophysiological interplay between muscle and nerve and supports the hypothesis that muscle is a source of signals that can either positively or negatively affect the nervous system.

No MeSH data available.


Related in: MedlinePlus