Neuroprotective Efficacy of Fisetin Against VPA-Induced Autistic Neurobehavioral Alterations by Targeting Dysregulated Redox Homeostasis

IF 2.8 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Molecular Neuroscience Pub Date : 2023-06-01 DOI:10.1007/s12031-023-02127-w

Sweety Mehra, Aitizaz Ul Ahsan, Madhu Sharma, Muskan Budhwar, Mani Chopra

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引用次数: 1

Abstract

Autism is a neurodevelopmental condition, and it's associated pathophysiology, viz., oxidative stress and altered cellular homeostasis, has been extensively intertwined with behavioral impairments. Therefore, targeting oxidative stress and redox cellular homeostasis could be beneficial in relieving autistic-like symptoms. For this purpose, we examined a library of nutraceutical compounds that led us to a bioflavonoid fisetin. Autism-like neurobehavior was induced by subjecting the pregnant rodents to valproic acid at the time of neural tube closure (GD12.5). In this novel study, fisetin was evaluated for its neuroprotective potential at gestational (GD13 until delivery) and post-weaning developmental windows (PND 23–32) in VPA-induced rodent model of autism. Developmental VPA exposure increased intracellular ROS production, oxidative stress, altered AChE and ATPases in brain regions, and induced autistic-like behavioral impairments (social, repetitive, stereotyped, and sensorimotor). The present findings suggested that gestational and post-weaning fisetin treatment significantly improved the behavioral impairments by attenuating elevated oxidative stress, ROS, lipid peroxidation, and re-establishing redox homeostasis. Also, it effectively reinstated the reduced levels of endogenous antioxidants, glutathione, AChE, and ATPases by its antioxidant potential. Therefore, fisetin with its properties could be used as a potential therapeutic agent in overcoming the symptoms associated with autism.

Graphical Abstract

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非西汀对vpa诱导的自闭症神经行为改变的神经保护作用

自闭症是一种神经发育疾病，它与病理生理学有关，即氧化应激和细胞稳态改变，与行为障碍密切相关。因此，靶向氧化应激和氧化还原细胞稳态可能有助于缓解自闭症样症状。为此，我们检查了一个营养化合物库，使我们找到了一种生物类黄酮非塞酮。在神经管闭合时给妊娠鼠丙戊酸诱导自闭症样神经行为(GD12.5)。在这项新的研究中，非瑟酮在vpa诱导的自闭症啮齿动物模型的妊娠期(GD13至分娩)和断奶后发育窗口(PND 23-32)评估了其神经保护潜力。发育性VPA暴露会增加细胞内ROS的产生、氧化应激、大脑区域乙酰胆碱酯酶和三磷酸腺苷酶的改变，并诱发自闭症样行为障碍(社交、重复、刻板印象和感觉运动)。目前的研究结果表明，妊娠期和断奶后非瑟酮治疗通过降低升高的氧化应激、ROS、脂质过氧化和重建氧化还原稳态，显著改善了行为障碍。此外，它有效地恢复内源性抗氧化剂，谷胱甘肽，乙酰胆碱酯酶和三磷酸腺苷酶通过其抗氧化潜力的降低水平。因此，非瑟酮可以作为一种潜在的治疗药物来克服自闭症相关的症状。图形抽象

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Molecular Neuroscience 医学-神经科学

CiteScore

6.60

自引率

3.20%

发文量

142

审稿时长

1 months

期刊介绍： The Journal of Molecular Neuroscience is committed to the rapid publication of original findings that increase our understanding of the molecular structure, function, and development of the nervous system. The criteria for acceptance of manuscripts will be scientific excellence, originality, and relevance to the field of molecular neuroscience. Manuscripts with clinical relevance are especially encouraged since the journal seeks to provide a means for accelerating the progression of basic research findings toward clinical utilization. All experiments described in the Journal of Molecular Neuroscience that involve the use of animal or human subjects must have been approved by the appropriate institutional review committee and conform to accepted ethical standards.