Brazilian Reproducibility Initiative in preclinical Systematic Review and Meta-Analysis (BRISA) Collaboration, Rio de Janeiro, RJ, Brazil.
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Syst Rev. 2022 Jul 26;11(1):150. doi: 10.1186/s13643-022-02028-w.
Autism spectrum disorder (ASD) is a neurodevelopmental condition associated with severe social communication, interaction, and sensory processing impairments. Efforts to understand its etiology and pathophysiology are crucial for improving treatment and prevention measures. Preclinical models of ASD are essential for investigating the biological mechanisms and should present translatability potential. We aim to evaluate the consistency of the most commonly used rodent models of ASD in displaying autistic-like behavior through a systematic review and meta-analysis.
This review will focus on the most frequently used autism models, surveying studies of six genetic (Ube3a, Pten, Nlgn3, Shank3, Mecp2, and Fmr1), three chemically induced (valproic acid (VPA), lipopolysaccharide (LPS), and polyinosinic:polycytidylic acid (poly(I:C))), and one inbred model (BTBR T+ Itpr3tf/J mouse strain). Two independent reviewers will screen the records. Data extraction of behavioral outcomes and risk of bias evaluation will be performed. We will conduct a meta-analysis whenever at least five studies investigate the same model and behavioral outcome. We will also explore the heterogeneity and publication bias. Network meta-analyses are planned to compare different models.
By shortening the gap between animal behavior and human endophenotypes or specific clinical symptoms, we expect to help researchers on which rodent models are adequate for research of specific behavioral manifestations of autism, which potentially require a combination of them depending on the research interest.
PROSPERO CRD42021226299 .
自闭症谱系障碍（ASD）是一种与严重社交沟通、互动和感官处理障碍相关的神经发育障碍。努力了解其病因和病理生理学对于改善治疗和预防措施至关重要。ASD 的临床前模型对于研究生物学机制至关重要，并且应该具有转化潜力。我们旨在通过系统评价和荟萃分析评估最常用于表现自闭症样行为的啮齿动物 ASD 模型的一致性。
本综述将重点关注最常用的自闭症模型，调查六种遗传（Ube3a、Pten、Nlgn3、Shank3、Mecp2 和 Fmr1）、三种化学诱导（丙戊酸（VPA）、脂多糖（LPS）和多聚肌苷酸：多聚胞苷酸（poly(I:C))）和一种近交模型（BTBR T+ Itpr3tf/J 小鼠品系）的研究。两名独立审查员将筛选记录。将进行行为结果和偏倚风险评估的数据提取。只有当至少有五项研究调查相同模型和行为结果时，我们才会进行荟萃分析。我们还将探索异质性和发表偏倚。计划进行网络荟萃分析以比较不同的模型。
通过缩短动物行为与人类表型或特定临床症状之间的差距，我们希望帮助研究人员确定哪些啮齿动物模型适合研究自闭症的特定行为表现，根据研究兴趣，这些模型可能需要组合使用。
PROSPERO CRD42021226299。
