大麻素受体CB1和CB2激活恢复海马脂质谱并减轻丙戊酸诱导的ASD大鼠自闭症样行为

IF 5 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics Pub Date : 2025-08-25 DOI:10.1111/cns.70591

Haoran Wang, Mengyuan Zhang, Sen Yang, Yi Jiang, Lijie Wu, Caihong Sun

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引用次数: 0

摘要

目的：新的证据表明，脂质代谢失调与自闭症谱系障碍（ASD）有关，内源性大麻素系统（大麻素受体CB1R/CB2R）与脂质稳态有关。本研究在丙戊酸（VPA）诱导的ASD大鼠模型中探讨CB1R/CB2R激活是否改善海马脂质代谢和ASD样行为。方法暴露于VPA （600 mg/kg, i.p）的雄性子代在出生后21 ~ 27天给予CB1R激动剂ACPA （0.1 mg/kg）或CB2R激动剂AM1241 （3 mg/kg）。asd样行为（大理石掩埋、自我梳理、社会互动、野外测试）和海马脂质谱（UPLC-MS/MS）分析。结果暴露于vpa的大鼠重复性行为、社交缺陷和多动症状明显增加，ACPA和AM1241均可显著缓解这些症状。脂质组学显示VPA大鼠海马磷脂酰胆碱、溶血磷脂酰胆碱、脂肪酸、鞘磷脂、神经酰胺和磷脂酰乙醇胺明显减少。两种激动剂均使血脂水平恢复到接近正常水平，与对照组相当。结论CB1R/CB2R激活可改善vpa诱导的ASD模型中的行为异常并纠正海马脂质失调，突出大麻素受体是ASD相关代谢紊乱的潜在治疗靶点。

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Cannabinoid Receptors CB1 and CB2 Activation Restores Hippocampal Lipid Profiles and Alleviates Autism-Like Behaviors in Valproic Acid-Induced ASD Rats

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Cannabinoid Receptors CB1 and CB2 Activation Restores Hippocampal Lipid Profiles and Alleviates Autism-Like Behaviors in Valproic Acid-Induced ASD Rats

Objective

Emerging evidence suggests lipid metabolism dysregulation contributes to autism spectrum disorders (ASD), with the endocannabinoid system (cannabinoid receptors CB1R/CB2R) implicated in lipid homeostasis. This study investigated whether CB1R/CB2R activation improves hippocampal lipid metabolism and ASD-like behaviors in a valproic acid (VPA)-induced ASD rat model.

Methods

Male offspring from dams exposed to VPA (600 mg/kg, i.p.) received the CB1R agonist ACPA (0.1 mg/kg) or the CB2R agonist AM1241 (3 mg/kg) from postnatal days 21–27. ASD-like behaviors (marble burying, self-grooming, social interaction, open-field tests) and hippocampal lipid profiles (UPLC-MS/MS) were analyzed.

Results

VPA-exposed rats displayed heightened repetitive behaviors, social deficits, and hyperactivity, all significantly alleviated by ACPA and AM1241. Lipidomics revealed marked reductions in hippocampal phosphatidylcholines, lysophosphatidylcholines, fatty acids, sphingomyelins, ceramides, and phosphatidylethanolamines in VPA rats. Both agonists restored lipid levels to near normal, comparable to controls.

Conclusions

CB1R/CB2R activation ameliorates behavioral abnormalities and rectifies hippocampal lipid dysregulation in VPA-induced ASD models, highlighting cannabinoid receptors as potential therapeutic targets for ASD-associated metabolic disturbances.

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来源期刊

CNS Neuroscience & Therapeutics 医学-神经科学

CiteScore

7.30

自引率

12.70%

发文量

240

审稿时长

2 months

期刊介绍： CNS Neuroscience & Therapeutics provides a medium for rapid publication of original clinical, experimental, and translational research papers, timely reviews and reports of novel findings of therapeutic relevance to the central nervous system, as well as papers related to clinical pharmacology, drug development and novel methodologies for drug evaluation. The journal focuses on neurological and psychiatric diseases such as stroke, Parkinson’s disease, Alzheimer’s disease, depression, schizophrenia, epilepsy, and drug abuse.