Differential effects of paclitaxel and platinum derivatives on primary cultured Schwann cells could be associated with the pathogenesis of peripheral neuropathy

2015 Fiscal Year Final Research Report

• Project/Area Number: 26893118
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Pharmacology in pharmacy
• Research Institution: Kyoto University
• Principal Investigator: Imai Satoshi 京都大学, 医学(系)研究科(研究院), 助教 (80468579)
• Project Period (FY): 2014-08-29 – 2016-03-31
• Keywords: 抗がん剤 / 末梢神経障害 / シュワン細胞 / 脱分化 / ミトコンドリア障害

Outline of Final Research Achievements

To address mechanism underlying chemotherapy-induced peripheral neuropathy (CIPN), we focused on major supportive roles of Schwann cells in the maintenance of peripheral nerve systems and evaluated the effects of anti-cancer agents on primary cultured rat Schwann cells. Treatment of primary cultured Schwann cells from rat sciatic nerves with either cisplatin or oxaliplatin induced cell toxicity accompanied with mitochondrial dysfunction even after the washout of each drug. On the contrary, the treatment with paclitaxel to Schwann cells reverted to immature state accompanied with its bipolar process retraction. After the washout of paclitaxel, immature Schwann cells differentiated into mature state. These phenomena can explain different mechanisms of chemotherapy-induced peripheral neuropathy depending on classes of anti-cancer agents. Furthermore, we propose here that such diverse effects of anti-cancer agents on Schwann cells are likely responsible for the development of CIPN.

Free Research Field

神経科学、神経薬理学、医療薬剤学