Sodium valproate ablates ferroptosis in kainic acid-induced epileptic seizure via suppressing lysyl oxidase.

IF 1.6 4区医学 Q4 NEUROSCIENCES

Neuroreport Pub Date : 2024-12-04 Epub Date: 2024-09-30 DOI:10.1097/WNR.0000000000002103

Qin Li, Yu-Han Huang, Qiu-Qi Li, Ji-Ning Jia, Zhao-Qian Liu, Hong-Hao Zhou, Xin-Yu Zhou, Wei-Lin Jin, Xiao-Yuan Mao

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Abstract

The objective of this study is to explore whether sodium valproate (VPA) alleviates epileptic seizures via suppressing lysyl oxidase (Lox)-mediated ferroptosis. Epileptic seizure mouse model was prepared via intrahippocampal injection of kainic acid (250 ng/μl). After treatment with kainic acid, VPA was injected intraperitoneally by the dose of 250 mg/kg twice daily for 4 days. Ferroptosis-associated indices including lipid peroxides (LPO) level and Ptgs2 mRNA in hippocampal tissue samples were detected. Additionally, effects of VPA on Lox mRNA and enzymatic activity were assessed by quantitative real-time PCR and a commercial kit, respectively. Neuronal survival was assessed by Nissl staining. In kainic acid-induced epileptic seizure mouse model, VPA significantly suppressed LPO level and Ptgs2 mRNA and the suppression of ferroptosis was positively correlated with its anti-seizure effect. Lox mRNA and enzymatic activity were also found to decrease in hippocampus of epileptic seizure mice after VPA treatment. Furthermore, overexpression of Lox via adeno-associated virus infection remarkably abrogated the inhibitory effect of VPA on ferroptosis and neuronal impairment together with its anti-seizure effect. VPA suppresses Lox-mediated ferroptosis process, which can provide the explanation for its anti-seizure property.

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丙戊酸钠通过抑制赖氨酰氧化酶消减凯尼酸诱导的癫痫发作中的铁突变。

本研究旨在探讨丙戊酸钠（VPA）是否能通过抑制赖氨酰氧化酶（Lox）介导的铁氧化作用来缓解癫痫发作。通过海马内注射凯尼酸（250 ng/μl）制备癫痫发作小鼠模型。凯尼酸治疗后，腹腔注射 VPA，剂量为 250 毫克/千克，每天两次，连续 4 天。检测海马组织样本中与铁中毒相关的指标，包括脂质过氧化物（LPO）水平和Ptgs2 mRNA。此外，VPA 对 Lox mRNA 和酶活性的影响分别通过实时定量 PCR 和商业试剂盒进行了评估。神经元存活率通过 Nissl 染色法进行评估。在凯尼酸诱导的癫痫发作小鼠模型中，VPA能显著抑制LPO水平和Ptgs2 mRNA，且对铁突变的抑制与其抗癫痫作用呈正相关。VPA 治疗后，癫痫小鼠海马中的 Lox mRNA 和酶活性也有所下降。此外，通过腺相关病毒感染过表达 Lox，可明显减弱 VPA 对铁卟啉沉积和神经元损伤的抑制作用，同时也减弱了其抗癫痫作用。VPA能抑制Lox介导的铁突变过程，这可以解释其抗癫痫特性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neuroreport 医学-神经科学

CiteScore

3.20

自引率

0.00%

发文量

150

审稿时长

1 months

期刊介绍： NeuroReport is a channel for rapid communication of new findings in neuroscience. It is a forum for the publication of short but complete reports of important studies that require very fast publication. Papers are accepted on the basis of the novelty of their finding, on their significance for neuroscience and on a clear need for rapid publication. Preliminary communications are not suitable for the Journal. Submitted articles undergo a preliminary review by the editor. Some articles may be returned to authors without further consideration. Those being considered for publication will undergo further assessment and peer-review by the editors and those invited to do so from a reviewer pool. The core interest of the Journal is on studies that cast light on how the brain (and the whole of the nervous system) works. We aim to give authors a decision on their submission within 2-5 weeks, and all accepted articles appear in the next issue to press.