Amelioration of propionic acid-induced autism-like behaviors in rats by fenofibrate: A focus on reduction of brain galectin-3 levels

IF 1.7 4区医学 Q3 DEVELOPMENTAL BIOLOGY International Journal of Developmental Neuroscience Pub Date : 2024-11-12 DOI:10.1002/jdn.10393

Mumin Alper Erdogan, Mine Ceren Akbulut, İlknur Altuntaş, Canberk Tomruk, Yiğit Uyanıkgil, Oytun Erbaş

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Abstract

Introduction

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interactions and repetitive behaviors. This study examines the effects of fenofibrate on a propionic acid (PPA)-induced rat model of ASD, focusing on behavioral changes, inflammatory markers, and histological findings.

Materials and Methods

Thirty male Wistar rats were divided into three groups: a control group, a group receiving PPA and saline, and a group treated with PPA and fenofibrate for 15 days. Behavioral assessments, including the three-chamber sociability test, open-field test, and passive avoidance learning, were conducted. Biochemical analyses measured TNF-α, NGF, IL-17, IL-2, and galectin-3 levels in brain tissues. Histological evaluations focused on Purkinje neuron counts in the cerebellum and neuronal changes in the CA1 and CA3 regions of the hippocampus, along with glial fibrillary acidic protein (GFAP) levels.

Results

Fenofibrate treatment significantly improved behavioral outcomes, reducing autism-like behaviors compared to the PPA/saline group. Biochemically, the PPA/saline group showed elevated levels of malondialdehyde, TNF-α, IL-2, IL-17, and galectin-3, which were reduced following fenofibrate treatment. Histologically, the PPA/saline group exhibited fewer, dysmorphic Purkinje neurons and increased glial activity in the CA1 region, both of which were ameliorated by fenofibrate treatment.

Conclusion

Fenofibrate shows promise in mitigating autism-like behaviors in a rat model of ASD, likely due to its antioxidative and neuroprotective properties, which contribute to preserving neuronal integrity and reducing inflammation.

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非诺贝特可改善丙酸诱发的大鼠自闭症样行为：重点关注降低脑部加连蛋白-3的水平。

简介自闭症谱系障碍（ASD）是一种以社会交往障碍和重复行为为特征的神经发育障碍。本研究探讨了非诺贝特对丙酸（PPA）诱导的自闭症谱系障碍大鼠模型的影响，重点关注行为变化、炎症标志物和组织学结果：将 30 只雄性 Wistar 大鼠分为三组：对照组、接受 PPA 和生理盐水治疗组以及接受 PPA 和非诺贝特治疗 15 天组。进行了行为评估，包括三室交际性测试、开阔地测试和被动回避学习。生化分析测定了脑组织中TNF-α、NGF、IL-17、IL-2和galectin-3的水平。组织学评估的重点是小脑中的Purkinje神经元数量、海马CA1和CA3区的神经元变化以及胶质纤维酸性蛋白（GFAP）水平：结果：与PPA/盐水组相比，非诺贝特治疗能明显改善行为结果，减少类似自闭症的行为。从生化角度看，PPA/盐水组的丙二醛、TNF-α、IL-2、IL-17和galectin-3水平升高，而非诺贝特治疗后这些水平降低。从组织学角度看，PPA/胰岛素组表现出更少、畸形的Purkinje神经元，CA1区神经胶质活动增加，非诺贝特治疗可改善这两种情况：非诺贝特有望减轻 ASD 大鼠模型中的自闭症样行为，这可能是由于非诺贝特具有抗氧化和神经保护特性，有助于保护神经元的完整性和减少炎症。

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来源期刊

International Journal of Developmental Neuroscience 医学-发育生物学

CiteScore

3.30

自引率

5.60%

发文量

审稿时长

6-12 weeks

期刊介绍： International Journal of Developmental Neuroscience publishes original research articles and critical review papers on all fundamental and clinical aspects of nervous system development, renewal and regeneration, as well as on the effects of genetic and environmental perturbations of brain development and homeostasis leading to neurodevelopmental disorders and neurological conditions. Studies describing the involvement of stem cells in nervous system maintenance and disease (including brain tumours), stem cell-based approaches for the investigation of neurodegenerative diseases, roles of neuroinflammation in development and disease, and neuroevolution are also encouraged. Investigations using molecular, cellular, physiological, genetic and epigenetic approaches in model systems ranging from simple invertebrates to human iPSC-based 2D and 3D models are encouraged, as are studies using experimental models that provide behavioural or evolutionary insights. The journal also publishes Special Issues dealing with topics at the cutting edge of research edited by Guest Editors appointed by the Editor in Chief. A major aim of the journal is to facilitate the transfer of fundamental studies of nervous system development, maintenance, and disease to clinical applications. The journal thus intends to disseminate valuable information for both biologists and physicians. International Journal of Developmental Neuroscience is owned and supported by The International Society for Developmental Neuroscience (ISDN), an organization of scientists interested in advancing developmental neuroscience research in the broadest sense.