Bhandari Ranjana, Kuhad Anurag
Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, UGC-Centre of Advanced Study, Panjab University, Chandigarh 160 014 India.
Neurochem Int. 2017 Feb;103:8-23. doi: 10.1016/j.neuint.2016.12.012. Epub 2016 Dec 23.
Neuronal dysfunction caused by neuroinflammation triggered by the stimulation of matrix metalloproteinases and the subsequent release of pro-inflammatory cytokines, as a result of oxidative stress and mitochondrial dysfunction, is one of the probable mechanisms involved in the pathogenesis of autism spectrum disorders (ASD). The aim of the present study was to explore the ameliorative potential of resveratrol on neuroinflammation in the experimental paradigm of neuroinflammatory model of ASD in rats.
1M Propanoic acid (PPA) (4 μl) was infused over 10 min into the anterior portion of the lateral ventricle to induce ASD like symptoms in rats. Resveratrol (5, 10 and 15 mg/kg) was administered starting from the 2nd day of the surgery and continued upto 28th day. Rats were tested for various behavioural paradigms such as social interaction, stereotypy, locomotor activity, anxiety, novelty, depression, spatial learning, memory, repetitive and pervasive behaviour between the 7th day and 28th day. In addition, biochemical tests for oxidative stress, mitochondrial complexes, TNF-α and MMP-9 were also assessed.
Treatment with resveratrol for four weeks restored, significantly and dose dependently, all the neurological, sensory, behavioural, biochemical and molecular deficits in PPA induced autistic phenotype in rats.
The major finding of the study is that resveratrol restored the core and associated symptoms of autistic phenotype by suppressing oxidative-nitrosative stress, mitochondrial dysfunction, TNF-α and MMP-9 expression in PPA induced ASD in rats. Therefore, resveratrol might serve as an adjunct potential therapeutic agent for amelioration of neurobehavioural and biochemical deficits associated with autism spectrum disorders.
基质金属蛋白酶刺激引发神经炎症，随后因氧化应激和线粒体功能障碍释放促炎细胞因子，由此导致的神经元功能障碍是自闭症谱系障碍（ASD）发病机制中可能涉及的机制之一。本研究的目的是在大鼠ASD神经炎症模型的实验范式中探索白藜芦醇对神经炎症的改善潜力。
将1M丙酸（PPA）（4μl）在10分钟内注入侧脑室前部，以诱导大鼠出现类似ASD的症状。从手术第二天开始给予白藜芦醇（5、10和15mg/kg），持续至第28天。在第7天至第28天期间，对大鼠进行各种行为范式测试，如社交互动、刻板行为、运动活动、焦虑、新奇性、抑郁、空间学习、记忆、重复和普遍行为。此外，还评估了氧化应激、线粒体复合物、TNF-α和MMP-9的生化测试。
白藜芦醇治疗四周后，显著且剂量依赖性地恢复了PPA诱导的大鼠自闭症表型中的所有神经、感觉、行为、生化和分子缺陷。
该研究的主要发现是，白藜芦醇通过抑制PPA诱导的大鼠ASD中的氧化亚硝化应激、线粒体功能障碍、TNF-α和MMP-9表达，恢复了自闭症表型的核心症状和相关症状。因此，白藜芦醇可能作为一种辅助潜在治疗剂，用于改善与自闭症谱系障碍相关的神经行为和生化缺陷。
