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Involvement of Charcot-Marie-Tooth disease gene mitofusin 2 expression in paclitaxel-induced mechanical allodynia in rats.

Authors: Yamashita, Yuta  Irie, Keiichi  Kochi, Akane  Kimura, Nami  Hayashi, Toshinobu  Matsuo, Koichi  Myose, Takayuki  Sano, Kazunori  Nakano, Takafumi  Takase, Yumi  Nakamura, Yoshihiko  Satho, Tomomitsu  Mishima, Kenji  Mishima, Kenichi 
Citation: Yamashita Y, etal., Neurosci Lett. 2017 Jun 3;653:337-340. doi: 10.1016/j.neulet.2017.05.069.
Pubmed: (View Article at PubMed) PMID:28587902
DOI: Full-text: DOI:10.1016/j.neulet.2017.05.069

Paclitaxel induces peripheral neuropathy, which is dose-limiting and results in loss of quality of life. Therefore, the prevention and treatment of paclitaxel-induced peripheral neuropathy are major concerns in clinical cancer therapy. However, the detailed mechanisms have not been fully elucidated. It has recently been reported that allelic variability in the Charcot-Marie-Tooth disease (CMT) genes, mitofusin 2 (MFN2), Rho guanine nucleotide exchange factor 10 (ARHGEF10), and periaxin (PRX), affected paclitaxel-induced peripheral neuropathy in clinical cases. Therefore, we hypothesized that paclitaxel may induce peripheral neuropathy due to changes in Mfn2, Arhgef10, and Prx mRNA expression. Paclitaxel (6mg/kg) was administered intraperitoneally, on two consecutive days per week for 4 weeks in rats. Paclitaxel-induced peripheral neuropathy was measured by the von Frey test and acetone test, mechanical allodynia, and cold hyperalgesia, respectively, on days 0, 3, 10, 17, and 24. Mfn2, Arhgef10, and Prx mRNA expression in the spinal cord were analyzed by qRT-PCR on days 3 and 24. Paclitaxel induced mechanical allodynia from days 17-24, but did not induce cold hyperalgesia. In addition, paclitaxel reduced Mfn2 mRNA expression, but not Arhgef10 or Prx mRNA expression, on days 3 and 24. In addition, Mfn2 mRNA level was decreased before the appearance of mechanical allodynia. The results of the present study suggest that a reduction in Mfn2 mRNA expression contributes to paclitaxel-induced mechanical allodynia.


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RGD Object Information
RGD ID: 12910704
Created: 2017-06-21
Species: All species
Last Modified: 2017-06-21
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.