Ferulic acid methylester improves the comorbidity of insomnia and anxiety in a rat model of PCPA-induced sleep disorder by activating DRN 5-HT neurons

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters Pub Date : 2025-05-27 DOI:10.1016/j.neulet.2025.138276

Quntao Li , Jingwen Zhai , Tongyu Du , Junjie He , Jingbin Zhang , Yuhe Tian , Ketao Ma , Junqiang Si , Jiangwen Yin , Yan Li

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引用次数: 0

Abstract

Objective

Previous studies have indicated that ferulic acid possesses sedative and hypnotic functions. As a derivative of ferulic acid, ferulic acid methylester (FAM) exhibits stronger activity and lower toxicity than ferulic acid. This study is intended to establish a rat model of insomnia induced by PCPA, with the aim of exploring the improvement effect of FAM on the comorbidity of anxiety and insomnia in PCPA-induced insomnia model rats and its underlying mechanisms.

Methods

Insomnia models were established by intraperitoneal injection of 400 mg/kg p-chlorophenylalanine (PCPA) in SD rats. FAM was administered at three doses: 10, 20, and 40 mg/kg. Anxiety levels were assessed using the elevated plus maze and open field tests. Sleep status was evaluated through 24-hour in vivo EEG monitoring. Immunofluorescence staining was used to observe changes in DRN 5-HT neuron activity. Chemogenetic techniques were employed to inhibit DRN 5-HT neurons to elucidate the underlying mechanism.

Results

Behavioral tests revealed that FAM at 20 mg/kg significantly reduced anxiety levels (P < 0.001) and increased total sleep time (P < 0.001). EEG recordings showed improved sleep structure, with increased NREM and REM sleep times. Immunofluorescence staining indicated increased activity of DRN 5-HT neurons following FAM treatment. Chemogenetic inhibition of DRN 5-HT neurons reversed the beneficial effects of FAM on anxiety and sleep, thereby confirming the involvement of these neurons in the mechanism of action of FAM.

Conclusions

Ferulic acid methylester improves comorbidity of anxiety and insomnia in PCPA-induced insomnia model rats by activating DRN 5-HT neurons.

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阿威酸甲基酯通过激活DRN 5-HT神经元改善pppa诱导的睡眠障碍大鼠模型中失眠和焦虑的共病。

目的：既往研究表明阿魏酸具有镇静、催眠作用。阿魏酸甲基lester （FAM）是阿魏酸的衍生物，具有较阿魏酸更强的活性和较低的毒性。本研究拟建立PCPA致失眠大鼠模型，探讨FAM对PCPA致失眠模型大鼠焦虑、失眠合并症的改善作用及其机制。方法：采用400 mg/kg对氯苯丙氨酸（PCPA）腹腔注射法建立SD大鼠失眠模型。FAM以三种剂量给药：10、20和40 mg/kg。焦虑水平评估采用高架加迷宫和野外测试。通过24小时体内脑电图监测评估睡眠状态。免疫荧光染色观察DRN 5-HT神经元活性变化。采用化学发生技术抑制DRN 5-HT神经元，以阐明其潜在机制。结果：行为学实验显示，FAM浓度为20 mg/kg显著降低焦虑水平（P ）。结论：阿威酸甲酯通过激活DRN 5-HT神经元改善pppa诱导的失眠模型大鼠的焦虑和失眠共病。

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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