长期服用低剂量阿司匹林可减轻丙戊酸暴露大鼠的 ASD 类行为并激活 AMPK

IF 2.2 4区医学 Q1 EDUCATION, SPECIAL

Research in Autism Spectrum Disorders Pub Date : 2024-10-01 DOI:10.1016/j.rasd.2024.102499

Yueting Zhang , Liyan Qin , Xufang Dai

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引用次数: 0

摘要

背景自闭症谱系障碍（ASD）是一种神经发育障碍，以社交沟通障碍和存在限制性/重复性行为为特征。自闭症的发病率在全球范围内呈上升趋势，但人们对自闭症的根本原因仍然缺乏足够的了解，目前也没有针对自闭症核心症状的药物干预措施。然而，最近的研究表明，阿司匹林有可能用于治疗 ASD。从出生后第 23 天到第 52 天，每天给雄性幼鼠注射低剂量阿司匹林（1 毫克/千克）或药物对照。通过社交互动、自发梳理试验、开阔地试验和光-暗转换来评估类似ASD的行为。结果长期服用低剂量阿司匹林可显著改善ASD大鼠的社会接近障碍，减少重复性梳理，缓解焦虑样行为。此外，服用阿司匹林还能激活暴露于 VPA 的大鼠海马中的 AMPK。

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Chronic administration of low dose aspirin alleviates ASD-like behaviors and activates AMPK in valproic acid-exposed rats

Background

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder distinguished by deficits in social communication and the presence of restricted/repetitive behaviors. There has been a global increase in the prevalence of ASD, yet the underlying causes of ASD remain inadequately understood, and there is currently no pharmacological intervention for the core symptoms of ASD. However, recent studies have suggested that aspirin may have the potential for use in the treatment of ASD.

Method

Pregnant rats were administered either VPA or normal saline on gestational day 12.5. The male pups were administered a low dose of aspirin (1 mg/kg) or a vehicle control daily from postnatal day 23 to day 52. ASD-like behaviors were assessed by social interaction, spontaneous grooming test, open field test and light-dark transitions. The activity of AMP-activated protein kinase (AMPK) was quantified by measuring the level of p-AMPK using an immunoblotting assay.

Results

Chronic administration of low dose aspirin resulted in significant improvements in social approach deficits, a reduction in repetitive grooming, and the alleviation of anxiety-like behavior in ASD rats. Furthermore, aspirin administration also led to the activation of AMPK in the hippocampus of rats exposed to VPA.

Conclusions

These results raise the question of the need for further investigation of agents with mechanisms related to aspirin in ASD.

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来源期刊

Research in Autism Spectrum Disorders Multiple-

CiteScore

4.20

自引率

8.00%

发文量

108

期刊介绍： Research in Autism Spectrum Disorders (RASD) publishes high quality empirical articles and reviews that contribute to a better understanding of Autism Spectrum Disorders (ASD) at all levels of description; genetic, neurobiological, cognitive, and behavioral. The primary focus of the journal is to bridge the gap between basic research at these levels, and the practical questions and difficulties that are faced by individuals with ASD and their families, as well as carers, educators and clinicians. In addition, the journal encourages submissions on topics that remain under-researched in the field. We know shamefully little about the causes and consequences of the significant language and general intellectual impairments that characterize half of all individuals with ASD. We know even less about the challenges that women with ASD face and less still about the needs of individuals with ASD as they grow older. Medical and psychological co-morbidities and the complications they bring with them for the diagnosis and treatment of ASD represents another area of relatively little research. At RASD we are committed to promoting high-quality and rigorous research on all of these issues, and we look forward to receiving many excellent submissions.