Cuminaldehyde, a Hopeful Agent, Mitigates Autistic-Like Behaviors, Combating Hippocampal Neuroinflammation in Maternal Separation Stress Model in Male Mice

IF 2.3 4区医学 Q2 DEVELOPMENTAL BIOLOGY

Developmental Neurobiology Pub Date : 2025-10-14 DOI:10.1002/dneu.23008

Alireza Gholipour Shahraki, Fariba Houshmand, Elham Saghaei, Hossein Amini-Khoei

{"title":"Cuminaldehyde, a Hopeful Agent, Mitigates Autistic-Like Behaviors, Combating Hippocampal Neuroinflammation in Maternal Separation Stress Model in Male Mice","authors":"Alireza Gholipour Shahraki, Fariba Houshmand, Elham Saghaei, Hossein Amini-Khoei","doi":"10.1002/dneu.23008","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background and aim</h3>\n \n <p>Autism spectrum disorder (ASD) is a neurodevelopmental disorder that appears in the earliest ages of the lifespan. The causes of ASD remain anonymous, although immunological, genetic, biological, and psychosocial theories have been proposed. Stresses during early life, such as maternal separation (MS), are one of the psychosocial causes of ASD. The neuroimmune response is complicated in the pathophysiology of ASD. Cuminaldehyde (CA) has different pharmacological effects, such as anti-inflammatory properties. This study aimed to explore effects of CA on autistic-like behaviors in maternally separated mice with respect to its probable anti-neuroinflammatory effects.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Forty male mice were randomly allocated to five groups, including control mice administered with normal saline, and MS groups received normal saline and CA with doses of 5, 25, 50 mg/kg intraperitoneally for 14 continuous days. The three-chamber sociability, the resident–intruder, and shuttle box tests were performed. Subsequently, mice were euthanized, and the expression of the <i>NLRP3</i>, <i>TLR4</i>, <i>HMGB1</i>, and <i>IL-1β</i> genes in the hippocampus was investigated using real-time PCR.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>MS mice showed diminished sociability preference, damaged passive avoidance memory, as well as aggressive behaviors. Behaviors related to autism in MS mice are associated with a rise in the expression of inflammatory markers in the hippocampus. CA reversed the deleterious effects of MS on behaviors, in addition to a decrease in the expression of inflammatory genes in the hippocampus.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>CA, via attenuation of neuroimmune reaction in the hippocampus, partially mitigated autistic-like behaviors in the MS mouse model.</p>\n </section>\n </div>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"85 4","pages":""},"PeriodicalIF":2.3000,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Developmental Neurobiology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/dneu.23008","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"DEVELOPMENTAL BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background and aim

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that appears in the earliest ages of the lifespan. The causes of ASD remain anonymous, although immunological, genetic, biological, and psychosocial theories have been proposed. Stresses during early life, such as maternal separation (MS), are one of the psychosocial causes of ASD. The neuroimmune response is complicated in the pathophysiology of ASD. Cuminaldehyde (CA) has different pharmacological effects, such as anti-inflammatory properties. This study aimed to explore effects of CA on autistic-like behaviors in maternally separated mice with respect to its probable anti-neuroinflammatory effects.

Methods

Forty male mice were randomly allocated to five groups, including control mice administered with normal saline, and MS groups received normal saline and CA with doses of 5, 25, 50 mg/kg intraperitoneally for 14 continuous days. The three-chamber sociability, the resident–intruder, and shuttle box tests were performed. Subsequently, mice were euthanized, and the expression of the NLRP3, TLR4, HMGB1, and IL-1β genes in the hippocampus was investigated using real-time PCR.

Results

MS mice showed diminished sociability preference, damaged passive avoidance memory, as well as aggressive behaviors. Behaviors related to autism in MS mice are associated with a rise in the expression of inflammatory markers in the hippocampus. CA reversed the deleterious effects of MS on behaviors, in addition to a decrease in the expression of inflammatory genes in the hippocampus.

Conclusion

CA, via attenuation of neuroimmune reaction in the hippocampus, partially mitigated autistic-like behaviors in the MS mouse model.

Abstract Image

查看原文本刊更多论文

Cuminaldehyde：一种有希望的药物，减轻自闭症样行为，对抗母体分离应激模型雄性小鼠海马神经炎症。

背景与目的：自闭症谱系障碍（ASD）是一种出现在生命早期的神经发育障碍。虽然已经提出了免疫学、遗传学、生物学和社会心理方面的理论，但自闭症的病因仍不清楚。早期生活中的压力，如母亲分离（MS），是ASD的社会心理原因之一。神经免疫反应在ASD的病理生理中是复杂的。孜然醛（CA）具有不同的药理作用，如抗炎特性。本研究旨在探讨CA对母分离小鼠自闭症样行为的影响及其可能的抗神经炎症作用。方法：将40只雄性小鼠随机分为5组，对照组小鼠灌胃生理盐水，MS组小鼠灌胃生理盐水和CA，剂量分别为5、25、50 mg/kg，连续灌胃14 d。进行了三室社交性、居住者-入侵者和穿梭箱测试。随后，对小鼠实施安乐死，采用real-time PCR检测海马NLRP3、TLR4、HMGB1和IL-1β基因的表达。结果：MS小鼠社交偏好降低，被动回避记忆受损，攻击行为受损。在多发性硬化症小鼠中，与自闭症相关的行为与海马体中炎症标志物表达的增加有关。CA逆转了MS对行为的有害影响，并减少了海马中炎症基因的表达。结论：CA通过减弱海马神经免疫反应，部分减轻了MS小鼠模型的自闭症样行为。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Developmental Neurobiology 生物-发育生物学

CiteScore

6.50

自引率

0.00%

发文量

审稿时长

4-8 weeks

期刊介绍： Developmental Neurobiology (previously the Journal of Neurobiology ) publishes original research articles on development, regeneration, repair and plasticity of the nervous system and on the ontogeny of behavior. High quality contributions in these areas are solicited, with an emphasis on experimental as opposed to purely descriptive work. The Journal also will consider manuscripts reporting novel approaches and techniques for the study of the development of the nervous system as well as occasional special issues on topics of significant current interest. We welcome suggestions on possible topics from our readers.