Programa de Pós-Graduação em Bioquímica e Bioprospecção - Laboratório de Neuroquímica, Inflamação e Câncer, Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas, Pelotas, Brazil.
Programa de Pós-Graduação em Bioquímica e Bioprospecção - Laboratório de Biomarcadores, Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas, Pelotas, Brazil.
Int J Dev Neurosci. 2020 Jun;80(4):287-302. doi: 10.1002/jdn.10025. Epub 2020 Apr 22.
Autism is a neuropathology characterized by behavioral disorders. Considering that oxidative stress is involved in the pathophysiology of this disease, we evaluated the effects of quercetin, a flavonoid with antioxidant and neuroprotective properties, in an experimental model of autism induced by valproic acid (VPA). Twelve pregnant female rats were divided into four groups (control, quercetin, VPA, and VPA+quercetin). Quercetin (50 mg/kg) was administered orally to the animals from gestational days 6.5 to 18.5, and VPA (800 mg/kg) was administered orally in a single dosage on gestational day 12.5. Behavioral tests such as open field, social interaction, and tail flick nociceptive assays were performed on pups between 30 and 40 days old, after which the animals were euthanized. Cerebral cortex, hippocampus, striatum, and cerebellum were collected for evaluation of oxidative stress parameters. The pups exposed to VPA during the gestational period showed reduced weight gain, increased latency in the open field and tail flick tests, reduced time of social interaction, accompanied by changes in oxidative stress parameters mainly in the hippocampus and striatum. Prenatal treatment with quercetin prevented the behavioral changes and damage caused by oxidative stress, possibly due to its antioxidant action. Our findings demonstrated that quercetin has neuroprotective effects in an animal model of autism, suggesting that this natural molecule could be an important therapeutic agent for treatment of autism spectrum disorders (ASDs).
自闭症是一种以行为障碍为特征的神经病理学。考虑到氧化应激参与了这种疾病的病理生理学,我们评估了槲皮素(一种具有抗氧化和神经保护特性的类黄酮)在丙戊酸(VPA)诱导的自闭症实验模型中的作用。12 只怀孕雌性大鼠被分为四组(对照组、槲皮素组、VPA 组和 VPA+槲皮素组)。从妊娠第 6.5 天到第 18.5 天,动物通过口服给予槲皮素(50mg/kg),在妊娠第 12.5 天,通过口服给予 VPA(800mg/kg)给予单次剂量。在 30 至 40 天大的幼崽中进行了行为测试,如旷场、社会互动和尾巴刺痛疼痛测试,之后对动物进行安乐死。收集大脑皮层、海马体、纹状体和小脑,以评估氧化应激参数。在妊娠期暴露于 VPA 的幼崽体重增加减少,旷场和尾巴刺痛测试的潜伏期增加,社会互动时间减少,同时主要在海马体和纹状体中氧化应激参数发生变化。产前用槲皮素治疗可预防行为变化和氧化应激引起的损伤,这可能是由于其抗氧化作用。我们的研究结果表明,槲皮素在自闭症动物模型中具有神经保护作用,这表明这种天然分子可能是治疗自闭症谱系障碍(ASD)的重要治疗剂。