Expression profiling of genes modulated by minocycline in a rat model of neuropathic pain

abstract: ...Background The molecular mechanisms underlying neuropathic pain are constantly being studied to create new opportunities to prevent or alleviate neuropathic pain. The aim of our study was to determine the gene expression changes induced by sciatic nerve chronic constriction injury (CCI) that are modulated by minocycline, which can effectively diminish neuropathic pain in animal studies. The genes associated with minocycline efficacy in neuropathic pain should provide insight into the etiology of neuropathic pain and identify novel therapeutic targets. Results We screened the ipsilateral dorsal part of the lumbar spinal cord of the rat CCI model for differentially expressed genes. Out of 22,500 studied transcripts, the abundance levels of 93 transcripts were altered following sciatic nerve ligation. Percentage analysis revealed that 54 transcripts were not affected by the repeated administration of minocycline (30mg/kg, i.p .), but the levels of 39 transcripts were modulated following minocycline treatment. We then selected two gene expression patterns, B1 and B2. The first transcription pattern, B1, consisted of 10 mRNA transcripts that increased in abundance after injury, and minocycline treatment reversed or inhibited the effect of the injury; the B2 transcription pattern consisted of 7 mRNA transcripts whose abundance decreased following sciatic nerve ligation, and minocycline treatment reversed the effect of the injury. Based on the literature, we selected seven genes for further analysis: Cd40 , Clec7a , Apobec3b , Slc7a7 , and Fam22f from pattern B1 and Rwdd3 and Gimap5 from pattern B2. Additionally, these genes were analyzed using quantitative PCR to determine the transcriptional changes strongly related to the development of neuropathic pain; the ipsilateral DRGs (L4-L6) were also collected and analyzed in these rats using qPCR. Conclusion In this work, we confirmed gene expression alterations previously identified by microarray analysis in the spinal cord and analyzed the expression of selected genes in the DRG. Moreover, we reviewed the literature to illustrate the relevance of these findings for neuropathic pain development and therapy. Further studies are needed to elucidate the roles of the individual genes in neuropathic pain and to determine the therapeutic role of minocycline in the rat neuropathic pain model.

... inhibited the effect of the injury; the B2 transcription pattern consisted of 7 mRNA transcripts whose abundance decreased following sciatic nerve ligation, and minocycline treatment reversed the effect of the injury. Based on the literature, we selected seven genes for further analysis: Cd40 , Clec7a , Apobec3b , Slc7a7 , and Fam22f from pattern B1 and Rwdd3 and Gimap5 from pattern B2. Additionally, these genes were analyzed using quantitative PCR to determine the transcriptional changes strongly

... administrations reduced the level of these changes. Transcription pattern B2 7.53% of 93 transcripts Seven transcripts ( Rwdd3 , LOC364991 , Gimap5 , RGD1305604 , Gpr110 , LOC287028 , and HeyI ) were characterized by a decrease in mRNA abundance following CCI, and minocycline administrations reduced the level of these changes. Transcription pattern B3 8.60% of 93 transcripts Eight transcripts ( RGD1559604 , Ms4a6a , Btg2 , LOC498606 , Wdr45 , Fn1 , Abt1 , and Pla1a ) were characterized by an increase in

... repeated treatment with minocycline significantly diminished the spinal level of Fam22f mRNA (from 2.40.3 to 1.40.2). In contrast, in the DRG (Figure 4 F), the downregulation of Fam22f mRNA (1.00.1 vs . 0.70.03) was observed compared to the nave rats, and repeated treatment with minocycline increased (from 0.70.03 to 0.80.03) the level of Fam22f . Genes from the B2 transcription pattern Genes similarly regulated by minocycline in the spinal cord and DRG Rwdd3 In the dorsal lumbar spinal cord, we observed compared to nave rats a slight downregulation of Rwdd3 mRNA (1.00.004 vs . 0.80.006) using microarray analysis (Figure 5 A), and repeated treatment with minocycline resulted in an increase (from 0.80.006 to 0.90.008) in the level of Rwdd3 mRNA. Figure 5 Genes from the B2 transcription pattern - similarly spinally and DRG regulated by minocycline. Comparison of the changes in the transcript levels of genes with expression pattern B2 ( Rwdd3 and Gimap5 ) in the lumbar spinal cord using

...<0.001 indicate a significant difference when compared to the V-CCI rats. Naive (N), vehicle (V; water for injection), minocycline (MC). qPCR analysis (Figure 5 B) confirmed the changes detected by microarray. In the spinal cord, Rwdd3 mRNA (1.00.006 vs . 0.80.05) was downregulated compared to the nave rats, and repeated treatment with minocycline significantly increased the level of Rwdd3 mRNA (from 0.80.05 to 1.00.08). In the DRG (Figure 5 C), Rwdd3 mRNA (1.00.006 vs . 0.750.02) was downregulated compared to the nave rats, and repeated treatment with minocycline did not influence the level of Rwdd3 (0.750.02 vs . 0.720.01). Gimap5 In the dorsal lumbar spinal cord, we observed compared to nave rats the downregulation of Gimap5 mRNA (1.00.01 vs . 0.70.003) using microarray analysis (Figure 5 D). Chronic treatment with minocycline decreased (from 0.70.003 to 0.80.02) the level of Gimap5 mRNA. qPCR analysis (Figure 5 E) confirmed the changes detected by microarray. In the spinal cord, the

... following injury, and minocycline administration reversed or inhibited the effect of the injury. The B2 transcription pattern contained 7 transcripts; the mRNA abundance levels of these genes decreased after sciatic nerve ligation, and minocycline administration reversed the effect of the injury. According to the literature, we selected the following genes for qPCR analysis: Cd40 , Clec7a , Apobec3b , Slc7a7 , and Fam22f from pattern B1 and Rwdd3 and Gimap5 from pattern B2. Cd40 , Clec7a and Apobec3b

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Gene: RWDD3 - RWD domain containing 3 - (NCBI)

Protein : 4y1l

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