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维生素A缺乏与补充对丙戊酸诱导的自闭症大鼠模型雄性后代行为及氧化应激标志物的影响

The Impact of Vitamin A Deficiency and Supplementation on Behavioral and Oxidative Stress Markers in Male Offspring of a Valproic Acid-Induced Autism Rat Model.

作者信息

Ezzahra Kacimi Fatima, Soumia Ed-Day, Habiba Nechchadi, Laila Ibouzineddine, Mhamed Ramchoun, Hicham Berrougui, Fatima-Zahra Azzaoui, Samira Boulbaroud

机构信息

Polydisciplinary Faculty, Biotechnology and Sustainable Development of Natural Resources Unit, Sultan Moulay Slimane University, Beni Mellal, Morocco.

Department of Biology, Faculty of Science, Unit of Neuroscience, Neuroimmunology and Behavior, Laboratory of Biology and Health, Ibn Tofail University, Kenitra, Morocco.

出版信息

Dev Neurobiol. 2025 Jul;85(3):e22990. doi: 10.1002/dneu.22990.

DOI:10.1002/dneu.22990
PMID:40620131
Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental condition influenced by genetic and environmental factors, including prenatal nutrition. This study investigates the role of Vitamin A deficiency (VAD) in exacerbating ASD-like behaviors in a valproic acid (VPA)-induced rat model and mitigating effects of Vitamin A supplementation (VAS). Twenty-five pregnant rats were divided into five groups, with treatments including VPA exposure and VAD. Neurodevelopmental and behavioral tests, such as the rollover, negative geotaxis, gait, and open field, assessed motor coordination and social interaction in offspring. VPA and VAD groups showed impaired behaviors, motor deficits, and elevated oxidative stress, marked by reduced superoxide dismutase, catalase, and glutathione levels, alongside increased malondialdehyde, nitrite oxide, and altered acetylcholine activity. VAS partially restored antioxidant defenses and alleviated behavioral symptoms. These findings highlight the exacerbating impact of VAD on ASD-like behaviors and the therapeutic potential of VAS in managing neurodevelopmental and biochemical alterations linked to ASD.

摘要

自闭症谱系障碍(ASD)是一种受遗传和环境因素影响的神经发育疾病,包括产前营养。本研究调查了维生素A缺乏(VAD)在丙戊酸(VPA)诱导的大鼠模型中加重自闭症样行为的作用,以及补充维生素A(VAS)的缓解效果。将25只怀孕大鼠分为五组,治疗方法包括VPA暴露和VAD。通过翻正反射、负趋地性、步态和旷场等神经发育和行为测试,评估后代的运动协调性和社交互动。VPA组和VAD组表现出行为受损、运动缺陷和氧化应激升高,表现为超氧化物歧化酶、过氧化氢酶和谷胱甘肽水平降低,同时丙二醛、一氧化氮增加,乙酰胆碱活性改变。VAS部分恢复了抗氧化防御并减轻了行为症状。这些发现突出了VAD对自闭症样行为的加剧影响,以及VAS在管理与ASD相关的神经发育和生化改变方面的治疗潜力。

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