Sphingosine-1-phosphate attenuates seizures and cognitive deficits, associated with reduced hippocampal IL-1β in a PTZ-induced epilepsy model

IF 2.2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters Pub Date : 2026-03-26 Epub Date: 2026-01-30 DOI:10.1016/j.neulet.2026.138527

Kai Luo , Weiwen Zeng , Qing Chen , Zhijian Ma , Shixiong Huang , Xinyu Ben

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引用次数: 0

Abstract

Background and aim

Epilepsy is a prevalent neurological disorder frequently accompanied by cognitive impairments and neuronal damage. Neuroinflammation—particularly mediated by interleukin-1β (IL-1β)—plays a critical role in epileptogenesis. Sphingosine-1-phosphate (S1P), a bioactive lipid mediator, has been implicated in neuroprotection and anti-inflammatory signaling; however, its role in epilepsy remains unclear. This study aimed to investigate the effects and underlying mechanisms of S1P in a pentylenetetrazol (PTZ)-induced mouse model of epilepsy.

Methods

Male C57BL/6 mice were administered PTZ (33 mg/kg, i.p.) every other day for a total of 15 injections to establish a seizure-kindling model. S1P (0.5 mg/mL) was administered intraperitoneally during the subsequent treatment period. Seizure activity was assessed using electroencephalographic (EEG) recordings. Cognitive function was evaluated with the Morris water maze. Hippocampal neuronal morphology was examined via Nissl staining. The expression levels of IL-1β mRNA and precursor protein in the hippocampus were measured by qRT-PCR and Western blotting, respectively.

Results

S1P treatment significantly reduced seizure frequency and amplitude, shortened seizure duration, and ameliorated EEG abnormalities in epileptic mice. In behavioral assays, S1P improved spatial learning and memory performance. Histological analysis demonstrated reduced neuronal degeneration and preservation of hippocampal architecture in S1P-treated epileptic mice. Furthermore, S1P markedly decreased hippocampal IL-1β expression at both the mRNA and protein levels.

Conclusions

S1P exerts anti-seizure and neuroprotective effects in PTZ-induced epileptic mice and attenuates IL-1β–mediated neuroinflammation. These findings suggest that the S1P–IL-1β axis may represent a promising therapeutic target for epilepsy and its associated cognitive impairments.

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在ptz诱导的癫痫模型中，鞘氨醇-1-磷酸减轻癫痫发作和认知缺陷，与海马IL-1β减少有关。

背景和目的：癫痫是一种常见的神经系统疾病，常伴有认知障碍和神经元损伤。神经炎症-特别是由白细胞介素-1β (IL-1β)介导-在癫痫发生中起关键作用。鞘氨醇-1-磷酸（S1P）是一种生物活性脂质介质，与神经保护和抗炎信号有关；然而，它在癫痫中的作用仍不清楚。本研究旨在探讨S1P在戊四氮唑（PTZ）诱导的小鼠癫痫模型中的作用及其机制。方法：雄性C57BL/6小鼠给予PTZ(33 mg/kg, ig)，每隔一天注射15次，建立癫痫-点火模型。在后续治疗期间腹腔注射S1P（0.5 mg/mL）。使用脑电图（EEG）记录评估癫痫发作活动。采用Morris水迷宫评估认知功能。尼氏染色观察海马神经元形态。采用qRT-PCR和Western blotting分别检测海马组织中IL-1β mRNA和前体蛋白的表达水平。结果：S1P治疗可显著降低癫痫小鼠癫痫发作频率和幅度，缩短癫痫发作持续时间，改善脑电图异常。在行为测试中，S1P改善了空间学习和记忆表现。组织学分析表明，s1p治疗的癫痫小鼠神经元变性减少，海马结构保留。此外，S1P在mRNA和蛋白水平上显著降低海马IL-1β的表达。结论：S1P对ptz诱导的癫痫小鼠具有抗癫痫和神经保护作用，可减轻il -1β介导的神经炎症。这些发现表明，S1P-IL-1β轴可能是癫痫及其相关认知障碍的一个有希望的治疗靶点。

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

Neuroscience Letters 医学-神经科学

CiteScore

5.20

自引率

0.00%

发文量

408

审稿时长

50 days

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