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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

KEGG pathways showing the number of transcripts up (right side bars with positive values) and down-regulated (left side bars with negative values). The figure is representative of the KEGG pathways (EASE score was set to 0.05) obtained from the GO terms list containing genes related to death, stress and mitochondrion that have been already mentioned in the ALS literature. The categories were composed by seven genes (Cell cycle), six genes (ErbB signaling pathway), five genes (Tryptophan metabolism and RIG-I-like receptor signaling pathway).
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Figure 4: KEGG pathways showing the number of transcripts up (right side bars with positive values) and down-regulated (left side bars with negative values). The figure is representative of the KEGG pathways (EASE score was set to 0.05) obtained from the GO terms list containing genes related to death, stress and mitochondrion that have been already mentioned in the ALS literature. The categories were composed by seven genes (Cell cycle), six genes (ErbB signaling pathway), five genes (Tryptophan metabolism and RIG-I-like receptor signaling pathway).

Mentions: The DAVID analysis of dysregulated genes related to Death, Stress and Mitochondrion shown in Table 3 are identified with 16 KEGG pathways (Table 4). Furthermore, those identified KEGG pathways that have been previously described in the literature as being related to ALS include RIG-I-like receptor signaling (2 down and 3 up-regulated genes; Figure 4), tryptophan metabolism (5 down-regulated genes; Figure 4), ErbB signaling (1 down and 5 up-regulated genes; Figure 4) and cell cycle (2 down and 5 up-regulated genes; Figure 4). Of note, Cancer, Small cell lung cancer, the Adipocytokine signaling pathway and Chronic myeloid leukemia pathways are likely not related to ALS and were not included in Table 4.


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)

KEGG pathways showing the number of transcripts up (right side bars with positive values) and down-regulated (left side bars with negative values). The figure is representative of the KEGG pathways (EASE score was set to 0.05) obtained from the GO terms list containing genes related to death, stress and mitochondrion that have been already mentioned in the ALS literature. The categories were composed by seven genes (Cell cycle), six genes (ErbB signaling pathway), five genes (Tryptophan metabolism and RIG-I-like receptor signaling pathway).
© Copyright Policy
Related In: Results  -  Collection

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

Figure 4: KEGG pathways showing the number of transcripts up (right side bars with positive values) and down-regulated (left side bars with negative values). The figure is representative of the KEGG pathways (EASE score was set to 0.05) obtained from the GO terms list containing genes related to death, stress and mitochondrion that have been already mentioned in the ALS literature. The categories were composed by seven genes (Cell cycle), six genes (ErbB signaling pathway), five genes (Tryptophan metabolism and RIG-I-like receptor signaling pathway).
Mentions: The DAVID analysis of dysregulated genes related to Death, Stress and Mitochondrion shown in Table 3 are identified with 16 KEGG pathways (Table 4). Furthermore, those identified KEGG pathways that have been previously described in the literature as being related to ALS include RIG-I-like receptor signaling (2 down and 3 up-regulated genes; Figure 4), tryptophan metabolism (5 down-regulated genes; Figure 4), ErbB signaling (1 down and 5 up-regulated genes; Figure 4) and cell cycle (2 down and 5 up-regulated genes; Figure 4). Of note, Cancer, Small cell lung cancer, the Adipocytokine signaling pathway and Chronic myeloid leukemia pathways are likely not related to ALS and were not included in Table 4.

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