Characterizing maternal isolation-induced ultrasonic vocalizations in a gene–environment interaction rat model for autism

IF 2.4 4区 心理学 Q2 BEHAVIORAL SCIENCES
Dorit Möhrle, Megan Yuen, Alice Zheng, Faraj L. Haddad, Brian L. Allman, Susanne Schmid
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引用次数: 1

Abstract

Deficits in social communication and language development belong to the earliest diagnostic criteria of autism spectrum disorders. Of the many risk factors for autism spectrum disorder, the contactin-associated protein-like 2 gene, CNTNAP2, is thought to be important for language development. The present study used a rat model to investigate the potential compounding effects of autism spectrum disorder risk gene mutation and environmental challenges, including breeding conditions or maternal immune activation during pregnancy, on early vocal communication in the offspring. Maternal isolation-induced ultrasonic vocalizations from Cntnap2 wildtype and knockout rats at selected postnatal days were analyzed for their acoustic, temporal and syntax characteristics. Cntnap2 knockout pups from heterozygous breeding showed normal numbers and largely similar temporal structures of ultrasonic vocalizations to wildtype controls, whereas both parameters were affected in homozygously bred knockouts. Homozygous breeding further exacerbated altered pitch and transitioning between call types found in Cntnap2 knockout pups from heterozygous breeding. In contrast, the effect of maternal immune activation on the offspring's vocal communication was confined to call type syntax, but left ultrasonic vocalization acoustic and temporal organization intact. Our results support the “double-hit hypothesis” of autism spectrum disorder risk gene–environment interactions and emphasize that complex features of vocal communication are a useful tool for identifying early autistic-like features in rodent models.

Abstract Image

在一个基因-环境相互作用的自闭症大鼠模型中表征母亲隔离诱导的超声波发声
社会沟通和语言发展的缺陷属于自闭症谱系障碍的最早诊断标准。在自闭症谱系障碍的许多风险因素中,接触相关蛋白样2基因CNTNAP2被认为对语言发育很重要。本研究使用大鼠模型来研究自闭症谱系障碍风险基因突变和环境挑战(包括繁殖条件或怀孕期间母体免疫激活)对后代早期语音交流的潜在复合效应。本研究分析了Cntnap2野生型和敲除型大鼠在特定出生日后母鼠分离诱导的超声发声的声学、时间和句法特征。杂合育种的Cntnap2基因敲除幼崽数量正常,超声发声的时间结构与野生型对照基本相似,而纯合育种的敲除幼崽这两个参数都受到影响。纯合子育种进一步加剧了在Cntnap2基因敲除幼崽中发现的音调改变和呼叫类型之间的过渡。相比之下,母体免疫激活对后代发声交流的影响仅限于呼叫类型语法,但超声波发声的声学和时间组织完好无损。我们的研究结果支持自闭症谱系障碍风险基因-环境相互作用的“双重打击假说”,并强调声音交流的复杂特征是识别啮齿动物模型早期自闭症样特征的有用工具。
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来源期刊
Genes Brain and Behavior
Genes Brain and Behavior 医学-行为科学
CiteScore
6.80
自引率
4.00%
发文量
62
审稿时长
4-8 weeks
期刊介绍: Genes, Brain and Behavior was launched in 2002 with the aim of publishing top quality research in behavioral and neural genetics in their broadest sense. The emphasis is on the analysis of the behavioral and neural phenotypes under consideration, the unifying theme being the genetic approach as a tool to increase our understanding of these phenotypes. Genes Brain and Behavior is pleased to offer the following features: 8 issues per year online submissions with first editorial decisions within 3-4 weeks and fast publication at Wiley-Blackwells High visibility through its coverage by PubMed/Medline, Current Contents and other major abstracting and indexing services Inclusion in the Wiley-Blackwell consortial license, extending readership to thousands of international libraries and institutions A large and varied editorial board comprising of international specialists.
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