BACKGROUND Serotonin (5-hydroxytryptamine, 5-HT) is a key modulatory neurotransmitter in the mammalian central nervous system (CNS) that plays an important role as a developmental signal. Several lines of evidence associate altered 5-HT signaling with psychopathology in humans, particularly neurodevelopmental disorders such as autism spectrum disorders (ASD). ASD are characterized by persistent social and communication deficits along with stereotyped and repetitive patterns of behavior, with all symptoms emerging early during development. METHODS Here, we employed a mouse model devoid of brain 5-HT due to the lack of the gene encoding tryptophan hydroxylase 2 (Tph2), the initial and rate-limiting enzyme of 5-HT synthesis in the CNS. Tph2 null mutant (Tph2 (-/-) ) mice show normal prenatal development; however, they display for yet unknown reasons severe growth retardation during the first postnatal weeks. We investigated, therefore, whether Tph2 (-/-) mice display deficits in isolation-induced ultrasonic vocalizations (USV) as pups during early life. Isolation-induced USV are the most commonly studied behavioral measure to assess developmental delays and communication deficits in rodent models for ASD, particularly as they serve an important communicative function in coordinating mother-pup interactions. RESULTS Tph2 (-/-) mouse pups displayed a clear deficit in the emission of isolation-induced USV, as compared to heterozygous and wildtype littermates, exactly during growth retardation onset, including reduced call numbers and deficits in call clustering and temporal organization. CONCLUSIONS The ultrasonic communication impairment displayed by Tph2 (-/-) mouse pups is likely to result in a deficient mother-infant interaction, presumably contributing to their growth retardation phenotype, and represents a prominent feature relevant to ASD.

中文翻译：

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缺乏脑5-羟色胺的小鼠幼鼠中隔离诱导的幼犬超声通信减少。

背景技术5-羟色胺（5-羟色胺，5-HT）是哺乳动物中枢神经系统（CNS）中的关键调节性神经递质，其作为发育信号起着重要作用。几项证据将5-HT信号改变与人类的精神病理学相关联，特别是神经发育障碍，例如自闭症谱系障碍（ASD）。ASD的特征是持续存在的社交和沟通缺陷，以及刻板和重复的行为模式，所有症状都在发展初期出现。方法在这里，由于缺乏编码色氨酸羟化酶2（Tph2）的基因，该模型没有大脑中的5-HT小鼠模型，色氨酸羟化酶2是中枢神经系统中5-HT合成的起始酶和限速酶。Tph2空突变体（Tph2（-/-））小鼠显示出正常的产前发育；然而，由于未知原因，它们在出生后的头几周显示出严重的发育迟缓。因此，我们调查了Tph2（-/-）小鼠在幼年时期是否表现出隔离诱导的超声发声（USV）缺陷。隔离诱导的USV是评估ASD啮齿动物模型中发育延迟和交流障碍的最常用的行为手段，尤其是它们在协调母鼠互动中起重要的交流作用时。结果与杂合子和野生型同窝幼仔相比，Tph2（-/-）小鼠幼仔在分离诱导的USV排放中表现出明显的赤字，恰好在生长迟缓发作期间，包括电话数量减少以及电话聚类和时间组织缺陷。