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Dysregulated expression of death, stress and mitochondrion related genes in the sciatic nerve of presymptomatic SOD1(G93A) mouse model of Amyotrophic Lateral Sclerosis.

Alves CJ, Maximino JR, Chadi G - Front Cell Neurosci (2015)

Bottom Line: Despite the involvement of Schwann cells in early neuromuscular disruption in ALS, detailed molecular events of a dying-back triggering are unknown.DAVID demonstrated the deregulated genes related to death, stress and mitochondrion, which allowed the identification of Cell cycle, ErbB signaling, Tryptophan metabolism and Rig-I-like receptor signaling as the most representative KEGG pathways.The protein-protein interaction networks based upon deregulated genes have identified the top hubs (TRAF2, H2AFX, E2F1, FOXO3, MSH2, NGFR, TGFBR1) and bottlenecks (TRAF2, E2F1, CDKN1B, TWIST1, FOXO3).

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Neuroregeneration Center, University of São Paulo School of Medicine São Paulo, Brazil.

ABSTRACT
Schwann cells are the main source of paracrine support to motor neurons. Oxidative stress and mitochondrial dysfunction have been correlated to motor neuron death in Amyotrophic Lateral Sclerosis (ALS). Despite the involvement of Schwann cells in early neuromuscular disruption in ALS, detailed molecular events of a dying-back triggering are unknown. Sciatic nerves of presymptomatic (60-day-old) SOD1(G93A) mice were submitted to a high-density oligonucleotide microarray analysis. DAVID demonstrated the deregulated genes related to death, stress and mitochondrion, which allowed the identification of Cell cycle, ErbB signaling, Tryptophan metabolism and Rig-I-like receptor signaling as the most representative KEGG pathways. The protein-protein interaction networks based upon deregulated genes have identified the top hubs (TRAF2, H2AFX, E2F1, FOXO3, MSH2, NGFR, TGFBR1) and bottlenecks (TRAF2, E2F1, CDKN1B, TWIST1, FOXO3). Schwann cells were enriched from the sciatic nerve of presymptomatic mice using flow cytometry cell sorting. qPCR showed the up regulated (Ngfr, Cdnkn1b, E2f1, Traf2 and Erbb3, H2afx, Cdkn1a, Hspa1, Prdx, Mapk10) and down-regulated (Foxo3, Mtor) genes in the enriched Schwann cells. In conclusion, molecular analyses in the presymptomatic sciatic nerve demonstrated the involvement of death, oxidative stress, and mitochondrial pathways in the Schwann cell non-autonomous mechanisms in the early stages of ALS.

No MeSH data available.


Related in: MedlinePlus

Venn diagram of differentially expressed genes related to Death, Stress and Mitochondrion categories in sciatic nerve (60-day-old) of SOD1G93A animals compared to wild-type controls by means of microarray experiments. The lists of genes of the enriched categories were obtained by means of DAVID tool based on Biological Process and Cellular Component Ontology (EASE score set to 0.05), which identified 112 differentially expressed genes in Death, 66 genes in Stress, and 143 genes in Mitochondrion categories. Venn diagram demonstrates genes which are common to Death and Stress (17 genes), Death and Mitochondrion (nine genes), and also Stress and Mitochondrion (nine genes). Three genes (Hspa1a, Prdx2, Rrm2b) were present in the three categories (Death, Stress, and Mitochondrion).
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Figure 3: Venn diagram of differentially expressed genes related to Death, Stress and Mitochondrion categories in sciatic nerve (60-day-old) of SOD1G93A animals compared to wild-type controls by means of microarray experiments. The lists of genes of the enriched categories were obtained by means of DAVID tool based on Biological Process and Cellular Component Ontology (EASE score set to 0.05), which identified 112 differentially expressed genes in Death, 66 genes in Stress, and 143 genes in Mitochondrion categories. Venn diagram demonstrates genes which are common to Death and Stress (17 genes), Death and Mitochondrion (nine genes), and also Stress and Mitochondrion (nine genes). Three genes (Hspa1a, Prdx2, Rrm2b) were present in the three categories (Death, Stress, and Mitochondrion).

Mentions: A VEEN diagram of those dysregulated genes related to Death and Stress and Mitochondrion showed 17 genes belonging to both Death and Stress groups of genes, 9 genes belonging to both Death and Mitochondrion groups of genes, 5 genes belonging to both Stress and Mitochondrion groups of genes, and finally 3 genes belonging to the three, Death, Stress, and Mitochondrion groups of genes (Figure 3).


Dysregulated expression of death, stress and mitochondrion related genes in the sciatic nerve of presymptomatic SOD1(G93A) mouse model of Amyotrophic Lateral Sclerosis.

Alves CJ, Maximino JR, Chadi G - Front Cell Neurosci (2015)

Venn diagram of differentially expressed genes related to Death, Stress and Mitochondrion categories in sciatic nerve (60-day-old) of SOD1G93A animals compared to wild-type controls by means of microarray experiments. The lists of genes of the enriched categories were obtained by means of DAVID tool based on Biological Process and Cellular Component Ontology (EASE score set to 0.05), which identified 112 differentially expressed genes in Death, 66 genes in Stress, and 143 genes in Mitochondrion categories. Venn diagram demonstrates genes which are common to Death and Stress (17 genes), Death and Mitochondrion (nine genes), and also Stress and Mitochondrion (nine genes). Three genes (Hspa1a, Prdx2, Rrm2b) were present in the three categories (Death, Stress, and Mitochondrion).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4555015&req=5

Figure 3: Venn diagram of differentially expressed genes related to Death, Stress and Mitochondrion categories in sciatic nerve (60-day-old) of SOD1G93A animals compared to wild-type controls by means of microarray experiments. The lists of genes of the enriched categories were obtained by means of DAVID tool based on Biological Process and Cellular Component Ontology (EASE score set to 0.05), which identified 112 differentially expressed genes in Death, 66 genes in Stress, and 143 genes in Mitochondrion categories. Venn diagram demonstrates genes which are common to Death and Stress (17 genes), Death and Mitochondrion (nine genes), and also Stress and Mitochondrion (nine genes). Three genes (Hspa1a, Prdx2, Rrm2b) were present in the three categories (Death, Stress, and Mitochondrion).
Mentions: A VEEN diagram of those dysregulated genes related to Death and Stress and Mitochondrion showed 17 genes belonging to both Death and Stress groups of genes, 9 genes belonging to both Death and Mitochondrion groups of genes, 5 genes belonging to both Stress and Mitochondrion groups of genes, and finally 3 genes belonging to the three, Death, Stress, and Mitochondrion groups of genes (Figure 3).

Bottom Line: Despite the involvement of Schwann cells in early neuromuscular disruption in ALS, detailed molecular events of a dying-back triggering are unknown.DAVID demonstrated the deregulated genes related to death, stress and mitochondrion, which allowed the identification of Cell cycle, ErbB signaling, Tryptophan metabolism and Rig-I-like receptor signaling as the most representative KEGG pathways.The protein-protein interaction networks based upon deregulated genes have identified the top hubs (TRAF2, H2AFX, E2F1, FOXO3, MSH2, NGFR, TGFBR1) and bottlenecks (TRAF2, E2F1, CDKN1B, TWIST1, FOXO3).

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Neuroregeneration Center, University of São Paulo School of Medicine São Paulo, Brazil.

ABSTRACT
Schwann cells are the main source of paracrine support to motor neurons. Oxidative stress and mitochondrial dysfunction have been correlated to motor neuron death in Amyotrophic Lateral Sclerosis (ALS). Despite the involvement of Schwann cells in early neuromuscular disruption in ALS, detailed molecular events of a dying-back triggering are unknown. Sciatic nerves of presymptomatic (60-day-old) SOD1(G93A) mice were submitted to a high-density oligonucleotide microarray analysis. DAVID demonstrated the deregulated genes related to death, stress and mitochondrion, which allowed the identification of Cell cycle, ErbB signaling, Tryptophan metabolism and Rig-I-like receptor signaling as the most representative KEGG pathways. The protein-protein interaction networks based upon deregulated genes have identified the top hubs (TRAF2, H2AFX, E2F1, FOXO3, MSH2, NGFR, TGFBR1) and bottlenecks (TRAF2, E2F1, CDKN1B, TWIST1, FOXO3). Schwann cells were enriched from the sciatic nerve of presymptomatic mice using flow cytometry cell sorting. qPCR showed the up regulated (Ngfr, Cdnkn1b, E2f1, Traf2 and Erbb3, H2afx, Cdkn1a, Hspa1, Prdx, Mapk10) and down-regulated (Foxo3, Mtor) genes in the enriched Schwann cells. In conclusion, molecular analyses in the presymptomatic sciatic nerve demonstrated the involvement of death, oxidative stress, and mitochondrial pathways in the Schwann cell non-autonomous mechanisms in the early stages of ALS.

No MeSH data available.


Related in: MedlinePlus