两种自闭症谱系障碍大鼠模型预测有效性的比较:行为研究

IF 3.4 3区 医学 Q2 NEUROSCIENCES Neurotoxicology Pub Date : 2024-05-17 DOI:10.1016/j.neuro.2024.05.002
C. Morel , J. Paoli , C. Camonin , N. Marchal , N. Grova , H. Schroeder
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引用次数: 0

摘要

丙戊酸模型已被证明能够重现在患者身上观察到的类似 ASD 的行为,目前已作为大鼠的 ASD 模型在构造、面部和预测性方面得到广泛验证。文献一致认为,在妊娠第 12 天单次接触 500 毫克/千克的 VPA 可诱导 ASD 表型,腹腔途径是最常用的方法。不过,也有一些研究通过口服途径重复暴露来验证这一模型。给药方式对诱导 ASD 表型可能非常重要,因此非常需要进行比较。我们比较了两种 ASD 模型,一种是在 GD12 时按体重 500 毫克/千克的剂量进行 IP 注射诱导,另一种是在 GD11 和 GD13 之间按体重 500 毫克/千克的剂量每天重复 PO 给药诱导。在发育阶段和幼年阶段,对后代的行为表型进行了评估,以确定ASD的核心症状(社交行为障碍、刻板/重复行为、感官/沟通障碍)以及作为合并症的焦虑症。VPA IP模型比PO模型诱导的ASD表型更符合文献资料。这些结果证实,给药方式和VPA暴露窗口期是诱导ASD表型的关键因素。有趣的是,在发育阶段,VPA对男女儿童的影响相似,而在生命后期则趋于不同。
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Comparison of predictive validity of two autism spectrum disorder rat models: Behavioural investigations

The valproic acid model has been shown to reproduce ASD-like behaviours observed in patients and is now widely validated for construct, face, and predictivity as ASD model in rat. The literature agrees on using a single exposition to 500 mg/kg of VPA at gestational day 12 to induce ASD phenotype with the intraperitoneal route being the most commonly used. However, some studies validated this model with repeated exposure by using oral route. The way of administration may be of great importance in the induction of the ASD phenotype and a comparison is greatly required. We compared two ASD models, one induced by a unique IP injection of 500 mg/kg of body weight at GD12 and the other one by repeated PO administration of 500 mg/kg of body weight/day between GD11 and GD13. The behavioural phenotypes of the offspring were assessed for the core signs of ASD (impaired social behaviour, stereotypical/repetitive behaviours, sensory/communication deficits) as well as anxiety as comorbidity, at developmental and juvenile stages in both sexes. The VPA IP model induced a more literature-compliant ASD phenotype than the PO one. These results confirmed that the mode of administration as well as the window of VPA exposure are key factors in the ASD-induction phenotype. Interestingly, the effects of VPA administration were similar at the developmental stage between both sexes and then tended to differ later in life.

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来源期刊
Neurotoxicology
Neurotoxicology 医学-毒理学
CiteScore
6.80
自引率
5.90%
发文量
161
审稿时长
70 days
期刊介绍: NeuroToxicology specializes in publishing the best peer-reviewed original research papers dealing with the effects of toxic substances on the nervous system of humans and experimental animals of all ages. The Journal emphasizes papers dealing with the neurotoxic effects of environmentally significant chemical hazards, manufactured drugs and naturally occurring compounds.
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