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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

Validation of selected factors by western blot analysis. Graphs and representative western blot for (A) Pmp 22 and (B) Mpz. White bar refers to wild type (Wt) and black bar to MLC/SOD1G93A (Tg). Values are expressed as mean ± SEM. *p < 0.05; **p < 0.005 compared to Wt (n = 5 for each group).
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Figure 3: Validation of selected factors by western blot analysis. Graphs and representative western blot for (A) Pmp 22 and (B) Mpz. White bar refers to wild type (Wt) and black bar to MLC/SOD1G93A (Tg). Values are expressed as mean ± SEM. *p < 0.05; **p < 0.005 compared to Wt (n = 5 for each group).

Mentions: In order to show changes in protein expression, as a result of altered microRNA/mRNA expression, we performed western blot analysis for Pmp22 and Mpz expression. We revealed a significant up-regulation of Pmp22 and Mpz proteins in the spinal cord of MLC/SOD1G93A compared to wild type littermates (Figure 3), further supporting the evidence that these factors are targets of specific microRNAs that control the denervation and reinnervation processes.


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)

Validation of selected factors by western blot analysis. Graphs and representative western blot for (A) Pmp 22 and (B) Mpz. White bar refers to wild type (Wt) and black bar to MLC/SOD1G93A (Tg). Values are expressed as mean ± SEM. *p < 0.05; **p < 0.005 compared to Wt (n = 5 for each group).
© Copyright Policy
Related In: Results  -  Collection

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

Figure 3: Validation of selected factors by western blot analysis. Graphs and representative western blot for (A) Pmp 22 and (B) Mpz. White bar refers to wild type (Wt) and black bar to MLC/SOD1G93A (Tg). Values are expressed as mean ± SEM. *p < 0.05; **p < 0.005 compared to Wt (n = 5 for each group).
Mentions: In order to show changes in protein expression, as a result of altered microRNA/mRNA expression, we performed western blot analysis for Pmp22 and Mpz expression. We revealed a significant up-regulation of Pmp22 and Mpz proteins in the spinal cord of MLC/SOD1G93A compared to wild type littermates (Figure 3), further supporting the evidence that these factors are targets of specific microRNAs that control the denervation and reinnervation processes.

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