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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, MusarĂ² 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

STRING analysis of pathway enrichment and interaction in the altered mRNAs of the MLC/SOD1G93A transgenic mice. Protein products of five modulated mRNAs (Drp2, Prx, Egr2, Mpz, and Pmp22) were involved in eight interactions.
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Figure 4: STRING analysis of pathway enrichment and interaction in the altered mRNAs of the MLC/SOD1G93A transgenic mice. Protein products of five modulated mRNAs (Drp2, Prx, Egr2, Mpz, and Pmp22) were involved in eight interactions.

Mentions: Functional annotation of differentially expressed genes was performed using the DAVID functional annotation tool, an integrated biological knowledge base and analytic tools aimed at systematically extracting biological meaning from large gene and protein lists (Huang da et al., 2009). Similar annotation contents were clustered into annotation group with biological meanings. The annotation results revealed that 2.6% of the gene list examined was consistent with OMIM disease categories, in particular 5 of 17 genes extracted were related to Charcot-Marie-Tooth disease. On the other hand, the gene ontology analysis revealed that 39.3% of all gene list are significantly involved in biological processes category, 36.7% are part of cell components, and 39.8% are associated with molecular function categories. The nine interesting genes mentioned above were spread out in all the categories examined. The functional annotation clustering was done using the default parameters, Mus musculus as background and classification stringency was set as medium. Table 4 shows that the significantly modulated genes were involved in 5 functional clusters containing functional annotation for extracellular region, neuron development and differentiation, axonogenesis, and neurological system process. A further functional analysis was performed using STRING, a web base tool to explore potential protein-protein interaction, confirming the interactions among Pmp22, Mpz, Prx, and Egr2 proteins (Figure 4).


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, MusarĂ² A - Front Cell Neurosci (2015)

STRING analysis of pathway enrichment and interaction in the altered mRNAs of the MLC/SOD1G93A transgenic mice. Protein products of five modulated mRNAs (Drp2, Prx, Egr2, Mpz, and Pmp22) were involved in eight interactions.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4664730&req=5

Figure 4: STRING analysis of pathway enrichment and interaction in the altered mRNAs of the MLC/SOD1G93A transgenic mice. Protein products of five modulated mRNAs (Drp2, Prx, Egr2, Mpz, and Pmp22) were involved in eight interactions.
Mentions: Functional annotation of differentially expressed genes was performed using the DAVID functional annotation tool, an integrated biological knowledge base and analytic tools aimed at systematically extracting biological meaning from large gene and protein lists (Huang da et al., 2009). Similar annotation contents were clustered into annotation group with biological meanings. The annotation results revealed that 2.6% of the gene list examined was consistent with OMIM disease categories, in particular 5 of 17 genes extracted were related to Charcot-Marie-Tooth disease. On the other hand, the gene ontology analysis revealed that 39.3% of all gene list are significantly involved in biological processes category, 36.7% are part of cell components, and 39.8% are associated with molecular function categories. The nine interesting genes mentioned above were spread out in all the categories examined. The functional annotation clustering was done using the default parameters, Mus musculus as background and classification stringency was set as medium. Table 4 shows that the significantly modulated genes were involved in 5 functional clusters containing functional annotation for extracellular region, neuron development and differentiation, axonogenesis, and neurological system process. A further functional analysis was performed using STRING, a web base tool to explore potential protein-protein interaction, confirming the interactions among Pmp22, Mpz, Prx, and Egr2 proteins (Figure 4).

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