Splice-variant specific knock-down of Neuregline 1 as a treatment for chemotherapy-induced peripheral neuropathy

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K08816
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55050:Anesthesiology-related
• Research Institution: Okayama University
• Principal Investigator: Matsuoka Yoshikazu 岡山大学, 大学病院, 助教 (20509434)
• Co-Investigator(Kenkyū-buntansha): 賀来 隆治 岡山大学, 医歯薬学域, 講師 (50444659)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 化学療法誘発性末梢神経障害

Outline of Final Research Achievements

Chemotherapy-induced peripheral neuropathy (CIPN) is a major adverse effect of the cancer therapy. This study was aimed to study the etiology of CIPN. Neuregline 1 is a glicoprotein and involved in neural regeneration, differenciation. We studied the involvement of Neuregline 1 in the development of CIPN using rat model of CIPN. The rats were injected Vincristin (VCR) intraperitoneally. Mechanical withdrawal thresholds (50% PWT) was assesed by up-down method with von Frey fillaments. VCR injection caused decrease of 50% PWT from day 7 to day 14. We quantitated Neureglin 1 splice variants mRNA in the dorsal root ganglion (DRG) of the rats on day 14. Neuregline 1 splice variatns 1, 2, 3 showed tendencies to decrease.

Free Research Field

麻酔科学

Academic Significance and Societal Importance of the Research Achievements

ガン治療の進歩は目覚ましいが、一方で問題となるのはその副作用である。抗癌剤の大きな副作用として末梢神経障害が挙げられる。主に手足のしびれや痛みにより生活の質を大きく損なうため、予防法や治療法の開発が望まれているが、現在のところ有効な治療法はまだ開発されていない。今回抗癌剤による末梢神経障害の原因について研究し、Neuregurin1遺伝子が末梢神経で減少傾向にあったことから更なる研究が望まれる。