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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 mRNAs by Real-time PCR. Graphs (A) Pmp 22 (B) Prx (C) Mpz (D) Opalin (E) Egr2. White bar refers to wild type (Wt) and black bar to MLC/SOD1G93A (Tg). Values are expressed as mean ± SEM. *p < 0.05 compared to Wt (n = 4 for each group).
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Figure 2: Validation of selected mRNAs by Real-time PCR. Graphs (A) Pmp 22 (B) Prx (C) Mpz (D) Opalin (E) Egr2. White bar refers to wild type (Wt) and black bar to MLC/SOD1G93A (Tg). Values are expressed as mean ± SEM. *p < 0.05 compared to Wt (n = 4 for each group).

Mentions: The microarray data, related to the expression of mRNA in the spinal cord of both wild type and MLC/SOD1G93A transgenic mice, were deposited in the GEO database (GSE69582) and the list of the selected significantly up-regulated and down-regulated genes (p < 0.05; FC > 1.5) is shown in Tables 2, 3 respectively. Among these genes, nine up-regulated transcripts are involved in the myelination process such as Peripheral myelin protein 22 (Pmp22), Myelin protein zero (Mpz), Periaxin (Prx), the Early growth response 2 (Egr2) genes, Desert hedgehog (Dhh), or encode for extracellular matrix molecules such as Matrilin 2 (Matn2), Gliomedin (Gldn), Claudin 19 (Cldn19), and Smoothelin (Smtn). Other relevant modulated genes include glycoproteins, such as Osteoglycin (Ogn) and dystroglicans, such as Dystrophin related protein 2 (Drp2), associated with the myelination process. The Mpz, Pmp22, Egr2, Prx mRNAs were selected for validation by qRT-PCR analysis and results are shown in Figure 2. Opalin, another gene associated to myelin structures, was down-regulated in the spinal cord of MLC/SOD1G93A transgenic mice, compared to wild type littermates (Table 3). Opalin is expressed specifically in late stage of oligodendrocyte differentiation and has been shown to be dramatically reduced in a hypomyelination mouse model (Jiang et al., 2013; Tsutsumi et al., 2014).


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 mRNAs by Real-time PCR. Graphs (A) Pmp 22 (B) Prx (C) Mpz (D) Opalin (E) Egr2. White bar refers to wild type (Wt) and black bar to MLC/SOD1G93A (Tg). Values are expressed as mean ± SEM. *p < 0.05 compared to Wt (n = 4 for each group).
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Related In: Results  -  Collection

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Figure 2: Validation of selected mRNAs by Real-time PCR. Graphs (A) Pmp 22 (B) Prx (C) Mpz (D) Opalin (E) Egr2. White bar refers to wild type (Wt) and black bar to MLC/SOD1G93A (Tg). Values are expressed as mean ± SEM. *p < 0.05 compared to Wt (n = 4 for each group).
Mentions: The microarray data, related to the expression of mRNA in the spinal cord of both wild type and MLC/SOD1G93A transgenic mice, were deposited in the GEO database (GSE69582) and the list of the selected significantly up-regulated and down-regulated genes (p < 0.05; FC > 1.5) is shown in Tables 2, 3 respectively. Among these genes, nine up-regulated transcripts are involved in the myelination process such as Peripheral myelin protein 22 (Pmp22), Myelin protein zero (Mpz), Periaxin (Prx), the Early growth response 2 (Egr2) genes, Desert hedgehog (Dhh), or encode for extracellular matrix molecules such as Matrilin 2 (Matn2), Gliomedin (Gldn), Claudin 19 (Cldn19), and Smoothelin (Smtn). Other relevant modulated genes include glycoproteins, such as Osteoglycin (Ogn) and dystroglicans, such as Dystrophin related protein 2 (Drp2), associated with the myelination process. The Mpz, Pmp22, Egr2, Prx mRNAs were selected for validation by qRT-PCR analysis and results are shown in Figure 2. Opalin, another gene associated to myelin structures, was down-regulated in the spinal cord of MLC/SOD1G93A transgenic mice, compared to wild type littermates (Table 3). Opalin is expressed specifically in late stage of oligodendrocyte differentiation and has been shown to be dramatically reduced in a hypomyelination mouse model (Jiang et al., 2013; Tsutsumi et al., 2014).

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