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Expression changes of microRNA-1 and its targets Connexin 43 and brain-derived neurotrophic factor in the peripheral nervous system of chronic neuropathic rats.

Neumann E, Hermanns H, Barthel F, Werdehausen R, Brandenburger T - Mol Pain (2015)

Bottom Line: Immunohistochemical staining revealed an endoneural abundancy of Cx43 in injured sciatic nerves which was absent after Sham operation.This study demonstrates that CCI leads to a regulation of miRNAs (miR-1) in the peripheral nervous system.This regulation is associated with alterations in the expression and localization of the miR-1 dependent pain-relevant proteins BDNF and Cx43.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Moorenstr. 5, 40225, Düsseldorf, Germany. Elena.neumann@med.uni-duesseldorf.de.

ABSTRACT

Background: MicroRNAs (miRNAs) are involved in the neuroplastic changes which induce and maintain neuropathic pain. However, it is unknown whether nerve injury leads to altered miRNA expression and modulation of pain relevant target gene expression within peripheral nerves. In the present study, expression profiles of miR-1 and the pain-relevant targets, brain derived neurotrophic factor (BDNF) and Connexin 43 (Cx43), were studied in peripheral neuropathic pain, which was induced by chronic constriction injury (CCI) of the sciatic nerve in rats. The expression of miR-1 was investigated in the sciatic nerve, dorsal root ganglion (DRG) and the ipsilateral spinal cord by qPCR. Changes of BDNF and Cx43 expression patterns were studied using qPCR, Western blot analysis, ELISA and immunohistochemistry.

Results: In sciatic nerves of naïve rats, expression levels of miR-1 were more than twice as high as in DRG and spinal cord. In neuropathic rats, CCI lead to a time-dependent downregulation of miR-1 in the sciatic nerve but not in DRG and spinal cord. Likewise, protein expression of the miR-1 targets BDNF and Cx43 was upregulated in the sciatic nerve and DRG after CCI. Immunohistochemical staining revealed an endoneural abundancy of Cx43 in injured sciatic nerves which was absent after Sham operation.

Conclusions: This study demonstrates that CCI leads to a regulation of miRNAs (miR-1) in the peripheral nervous system. This regulation is associated with alterations in the expression and localization of the miR-1 dependent pain-relevant proteins BDNF and Cx43. Further studies will have to explore the function of miRNAs in the context of neuropathic pain in the peripheral nervous system.

No MeSH data available.


Related in: MedlinePlus

qPCR data of Cx43 mRNA expression in a peripheral nerve, where Cx43 is differentially expressed at three different time points and b DRG, where Cx43 is downregulated 6 days after CCI. c DRG: qPCR data of BDNF mRNA expression shows an upregulation 24 h and 6 days post CCI. Mean ± SD, *p < 0.05 vs. Sham.
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Fig4: qPCR data of Cx43 mRNA expression in a peripheral nerve, where Cx43 is differentially expressed at three different time points and b DRG, where Cx43 is downregulated 6 days after CCI. c DRG: qPCR data of BDNF mRNA expression shows an upregulation 24 h and 6 days post CCI. Mean ± SD, *p < 0.05 vs. Sham.

Mentions: The expression of Cx43 mRNA in the sciatic nerve was increased 4 h (relative expression 1.57 vs. Sham, p < 0.05), 24 h (relative expression 2.00 vs. Sham, p < 0.05) and 6 days (relative expression 2.78 vs. Sham, p < 0.05) post CCI surgery. After 12 days (relative expression 1.59 vs. Sham, p = 0.139) the relative expression of Cx43 mRNA declined to a not significant level (Figure 4a) compared to early expression. mRNA levels of BDNF in sciatic nerves of Sham-treated animals could not be detected using qPCR. In injured nerves of CCI rats however, mRNA of BDNF was detectable (data not shown).Figure 4


Expression changes of microRNA-1 and its targets Connexin 43 and brain-derived neurotrophic factor in the peripheral nervous system of chronic neuropathic rats.

Neumann E, Hermanns H, Barthel F, Werdehausen R, Brandenburger T - Mol Pain (2015)

qPCR data of Cx43 mRNA expression in a peripheral nerve, where Cx43 is differentially expressed at three different time points and b DRG, where Cx43 is downregulated 6 days after CCI. c DRG: qPCR data of BDNF mRNA expression shows an upregulation 24 h and 6 days post CCI. Mean ± SD, *p < 0.05 vs. Sham.
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4482165&req=5

Fig4: qPCR data of Cx43 mRNA expression in a peripheral nerve, where Cx43 is differentially expressed at three different time points and b DRG, where Cx43 is downregulated 6 days after CCI. c DRG: qPCR data of BDNF mRNA expression shows an upregulation 24 h and 6 days post CCI. Mean ± SD, *p < 0.05 vs. Sham.
Mentions: The expression of Cx43 mRNA in the sciatic nerve was increased 4 h (relative expression 1.57 vs. Sham, p < 0.05), 24 h (relative expression 2.00 vs. Sham, p < 0.05) and 6 days (relative expression 2.78 vs. Sham, p < 0.05) post CCI surgery. After 12 days (relative expression 1.59 vs. Sham, p = 0.139) the relative expression of Cx43 mRNA declined to a not significant level (Figure 4a) compared to early expression. mRNA levels of BDNF in sciatic nerves of Sham-treated animals could not be detected using qPCR. In injured nerves of CCI rats however, mRNA of BDNF was detectable (data not shown).Figure 4

Bottom Line: Immunohistochemical staining revealed an endoneural abundancy of Cx43 in injured sciatic nerves which was absent after Sham operation.This study demonstrates that CCI leads to a regulation of miRNAs (miR-1) in the peripheral nervous system.This regulation is associated with alterations in the expression and localization of the miR-1 dependent pain-relevant proteins BDNF and Cx43.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Moorenstr. 5, 40225, Düsseldorf, Germany. Elena.neumann@med.uni-duesseldorf.de.

ABSTRACT

Background: MicroRNAs (miRNAs) are involved in the neuroplastic changes which induce and maintain neuropathic pain. However, it is unknown whether nerve injury leads to altered miRNA expression and modulation of pain relevant target gene expression within peripheral nerves. In the present study, expression profiles of miR-1 and the pain-relevant targets, brain derived neurotrophic factor (BDNF) and Connexin 43 (Cx43), were studied in peripheral neuropathic pain, which was induced by chronic constriction injury (CCI) of the sciatic nerve in rats. The expression of miR-1 was investigated in the sciatic nerve, dorsal root ganglion (DRG) and the ipsilateral spinal cord by qPCR. Changes of BDNF and Cx43 expression patterns were studied using qPCR, Western blot analysis, ELISA and immunohistochemistry.

Results: In sciatic nerves of naïve rats, expression levels of miR-1 were more than twice as high as in DRG and spinal cord. In neuropathic rats, CCI lead to a time-dependent downregulation of miR-1 in the sciatic nerve but not in DRG and spinal cord. Likewise, protein expression of the miR-1 targets BDNF and Cx43 was upregulated in the sciatic nerve and DRG after CCI. Immunohistochemical staining revealed an endoneural abundancy of Cx43 in injured sciatic nerves which was absent after Sham operation.

Conclusions: This study demonstrates that CCI leads to a regulation of miRNAs (miR-1) in the peripheral nervous system. This regulation is associated with alterations in the expression and localization of the miR-1 dependent pain-relevant proteins BDNF and Cx43. Further studies will have to explore the function of miRNAs in the context of neuropathic pain in the peripheral nervous system.

No MeSH data available.


Related in: MedlinePlus