Differences in the ultrastructure of neurons in the spinal ganglion and dorsal rootlet between rats treated with cisplatin only versus co-administration with a sphingosine 1-phosphate receptor 2 agonist in attenuating neuropathy and allodynia

IF 3.9 3区医学 Q1 CLINICAL NEUROLOGY Journal of the Peripheral Nervous System Pub Date : 2023-07-22 DOI:10.1111/jns.12582

Kanokporn Chayaburakul, Wei Yi Ong, Deron R. Herr, Phetnarin Kobutree, Kraisri Chantra

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Abstract

Background and Aims

Cisplatin is a chemotherapeutic agent for many types of cancer. The neurotoxicity of cisplatin includes neuropathy and allodynia. We aimed to study structural changes by using CYM54-78, attenuating cisplatin-induced neuropathy and blocking the pathogenesis in neurons, and promoting axonal regeneration.

Methods

TEM (transmission electron microscopy) was used to distinguish ultrastructural changes in dorsal root ganglion (DRG) and dorsal rootlets (DR) between rats treated with cisplatin alone and rats co-treated with cisplatin and sphingosine -1-phosphate receptor2 (S1P2) agonist, CYM-5478.

Results

In DRG of rats treated with cisplatin alone, TEM micrographs showed necrosis and apoptotic cells. Neuronal cytoplasm showed numerous vacuole (stage C) and swelling (stage B➔C) mitochondrial degeneration. Neurons in DRG from cisplatin+CYM-5478 group showed a higher percentage of healthy mitochondria (from 5.3% to 75.6%) than those treated with cisplatin alone. DR of cisplatin only group showed abnormal axoplasm, axolemma, and focal detached myelin sheaths, especially in Aδ (fast pain) and Aβ (touch) fibers, and revealed collateral branches that sprouted from Aβ fibers, which is characteristic of allodynia. Moreover, vasoconstriction was observed in DRG and DR. Rats in cisplatin+CYM-5478 group showed not only fewer abnormal structures than those in cisplatin only group, but also showed Bands of Büngner and onion bulb-like structures, which are characteristic of nerve regeneration.

Interpretation

Together with our previous study, showed that CYM-5478 attenuated neuropathy and allodynia in a rat model of cisplatin-induced neuropathy, these results suggest S1P2 agonists as a potential approach the for treatment of cancer due to the reduction of side effects of cisplatin.

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单用顺铂与联用鞘氨醇1-磷酸受体2激动剂减轻神经病变和异常性疼痛大鼠脊髓神经节和背根神经元超微结构差异

背景与目的顺铂是一种治疗多种癌症的化疗药物。顺铂的神经毒性包括神经病变和异常性疼痛。我们的目的是研究CYM54-78的结构变化，减轻顺铂诱导的神经病变，阻断神经元的发病机制，促进轴突再生。方法采用透射电镜(TEM)观察顺铂单用和与鞘氨醇-1-磷酸受体2 (S1P2)激动剂CYM-5478联用大鼠背根神经节(DRG)和背根小管(DR)超微结构的变化。结果单用顺铂处理大鼠DRG后，透射电镜观察到细胞坏死和凋亡。神经元细胞质显示大量液泡(C期)和肿胀(B期)线粒体变性。顺铂+CYM-5478组DRG神经元的健康线粒体百分比(从5.3%到75.6%)高于单独顺铂组。单用顺铂组DR表现为轴质、轴膜、局灶性髓鞘异常，特别是Aδ(快痛)纤维和Aβ(触)纤维异常，并可见Aβ纤维长出侧支，为异位性痛的特征。同时，DRG和dr血管收缩，顺铂+CYM-5478组大鼠不仅异常结构少于单顺铂组，而且还出现了神经再生特征的带状带状结构和洋葱鳞茎样结构。结合我们之前的研究表明，CYM-5478在顺铂诱导的神经病变大鼠模型中减轻了神经病变和异常性疼痛，这些结果表明，由于减少了顺铂的副作用，S1P2激动剂可能成为治疗癌症的潜在途径。

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来源期刊

Journal of the Peripheral Nervous System 医学-临床神经学

CiteScore

6.10

自引率

7.90%

发文量

审稿时长

>12 weeks

期刊介绍： The Journal of the Peripheral Nervous System is the official journal of the Peripheral Nerve Society. Founded in 1996, it is the scientific journal of choice for clinicians, clinical scientists and basic neuroscientists interested in all aspects of biology and clinical research of peripheral nervous system disorders. The Journal of the Peripheral Nervous System is a peer-reviewed journal that publishes high quality articles on cell and molecular biology, genomics, neuropathic pain, clinical research, trials, and unique case reports on inherited and acquired peripheral neuropathies. Original articles are organized according to the topic in one of four specific areas: Mechanisms of Disease, Genetics, Clinical Research, and Clinical Trials. The journal also publishes regular review papers on hot topics and Special Issues on basic, clinical, or assembled research in the field of peripheral nervous system disorders. Authors interested in contributing a review-type article or a Special Issue should contact the Editorial Office to discuss the scope of the proposed article with the Editor-in-Chief.