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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 miRNAs array data by Real-time PCR. Graphs indicate relative expression of (A) mir-133a (B) mir-133b (C) mir-9 (D) mir-29 (E) mir-330 (F) mir-1. White bar refers to wild type (Wt) and black bar to MLC/SOD1G93A (Tg). Values are expressed as mean ± SEM. *p < 0.05 (n = 10 for each group).
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Figure 1: Validation of selected miRNAs array data by Real-time PCR. Graphs indicate relative expression of (A) mir-133a (B) mir-133b (C) mir-9 (D) mir-29 (E) mir-330 (F) mir-1. White bar refers to wild type (Wt) and black bar to MLC/SOD1G93A (Tg). Values are expressed as mean ± SEM. *p < 0.05 (n = 10 for each group).

Mentions: First, to identify deregulated miRNAs and transcripts in the spinal cord of MLC/SOD1G93A transgenic mice we performed miRNA expression profiling and DNA microarray, using the Taqman array card and Affymetrix Mouse Gene 2.0 ST respectively (GSE71194). Among the analyzed miRNAs, 54 were significantly down-regulated (p < 0.05) in the spinal cord of MLC/SOD1G93A transgenic mice compared to wild type littermates (Table 1). Of note, the miRnome profiling revealed the down regulation of mir-330, mir-133, and mir-1, which are involved in denervation and reinnervation processes (Jeng et al., 2009; Tsutsumi et al., 2014). In addition mir-29 and mir-9 family member were downregulated and their deregulation was associated with different neurodegenerative diseases, including Huntington, Alzheimer, and Parkinson diseases (Saito and Saito, 2012; Tsutsumi et al., 2014) and demyelination-related diseases (Li and Yao, 2012; Tsutsumi et al., 2014). Real time PCR analysis was performed to validate the expression of these relevant miRNAs in the spinal cord of both wild type and MLC/SOD1G93A transgenic mice (Figure 1).


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 miRNAs array data by Real-time PCR. Graphs indicate relative expression of (A) mir-133a (B) mir-133b (C) mir-9 (D) mir-29 (E) mir-330 (F) mir-1. White bar refers to wild type (Wt) and black bar to MLC/SOD1G93A (Tg). Values are expressed as mean ± SEM. *p < 0.05 (n = 10 for each group).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4664730&req=5

Figure 1: Validation of selected miRNAs array data by Real-time PCR. Graphs indicate relative expression of (A) mir-133a (B) mir-133b (C) mir-9 (D) mir-29 (E) mir-330 (F) mir-1. White bar refers to wild type (Wt) and black bar to MLC/SOD1G93A (Tg). Values are expressed as mean ± SEM. *p < 0.05 (n = 10 for each group).
Mentions: First, to identify deregulated miRNAs and transcripts in the spinal cord of MLC/SOD1G93A transgenic mice we performed miRNA expression profiling and DNA microarray, using the Taqman array card and Affymetrix Mouse Gene 2.0 ST respectively (GSE71194). Among the analyzed miRNAs, 54 were significantly down-regulated (p < 0.05) in the spinal cord of MLC/SOD1G93A transgenic mice compared to wild type littermates (Table 1). Of note, the miRnome profiling revealed the down regulation of mir-330, mir-133, and mir-1, which are involved in denervation and reinnervation processes (Jeng et al., 2009; Tsutsumi et al., 2014). In addition mir-29 and mir-9 family member were downregulated and their deregulation was associated with different neurodegenerative diseases, including Huntington, Alzheimer, and Parkinson diseases (Saito and Saito, 2012; Tsutsumi et al., 2014) and demyelination-related diseases (Li and Yao, 2012; Tsutsumi et al., 2014). Real time PCR analysis was performed to validate the expression of these relevant miRNAs in the spinal cord of both wild type and MLC/SOD1G93A transgenic mice (Figure 1).

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