Social peers rescue autism-relevant sociability deficits in adolescent mice.
Social peers rescue autism-relevant sociability deficits in adolescent mice.
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DOI：
10.1002/aur.163
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发表时间：
2011-02
期刊：
影响因子：
4.7
通讯作者：
Crawley, Jacqueline N.
中科院分区：
文献类型：
--
作者：
Yang, Mu;Perry, Kayla;Weber, Michael D.;Katz, Adam M.;Crawley, Jacqueline N.
有限的互惠社会互动是诊断自闭症的核心。行为干预计划在提高自闭症儿童的社交和沟通技能方面是有效的。我们正在使用老鼠模型来理解有效改善社会互动的行为干预的个别组成部分。BTBR T+Tf/J(BTBR)是一种近交系小鼠，表现出多个社会缺陷、异常发声和高水平的重复行为，这些与自闭症的所有三种诊断症状类别都相关。C57BL/6J(B6)系近交系小鼠，具有较高的社会性和较低的重复行为。我们推断，这些具有低社交互动和高社交互动的小鼠品系可能有助于评估作为青春期行为干预的社交同伴充实。同性别的幼年BTBR和B6被放在同一个家庭笼子里，作为笼子一起生活，直到它们成年。两个对照组是幼年B6和幼年BTBR一起居住。与B6笼子生活在一起的B6对照组显示出他们典型的高度社交能力。与BTBR笼子生活在一起的BTBR对照组显示出他们典型的低社交能力。值得注意的是，与B6共用笼子的BTBR在年轻时表现出很高的社交能力。同伴养育20天或40天同样有效。这些来自健壮的自闭症小鼠模型的结果支持了早期行为干预的策略，以治疗自闭症谱系障碍的社会领域，包括与社会同龄人的有益互动。科学摘要行为疗法是目前治疗自闭症诊断症状最有效的干预措施。我们利用自闭症的小鼠模型来评估改善小鼠社交能力的行为干预的组成部分。BTBR T+Tf/J(BTBR)是一种近交系小鼠，表现出显著的行为表型，对自闭症的所有三种诊断症状类别都具有表面有效性，包括在社交方式和互惠社交方面的健壮和良好复制的缺陷。为了探讨同伴互动在社交能力发展中的作用，将BTBR幼鼠与高度社会化近交系C57BL/6J(B6)幼鼠饲养在同一笼中。受试者小鼠在成年后接受了社交能力和重复行为的测试。用B6饲养的B6对照组表现出典型的高社交能力。用BTBR笼子饲养的BTBR对照组显示出它们的菌株-典型的缺乏社交能力。相比之下，在青少年时期用B6饲养的BTBR在年轻时表现出显著的社交能力。在改善社交行为方面，20天的干预与40天的干预同样有效。BTBR的高水平重复性自我修饰不能通过B6的同伴养育来挽救，这表明干预对社会领域的特异性。这些来自强健的自闭症小鼠模型的结果支持了这样的解释，即与青少年同龄人一起丰富社交是一种有益的干预措施，有助于改善成人在社交领域的结果。这一新的范式可能被证明有助于发现有效的行为治疗所必需的因素，以及有效的行为干预背后的生物学机制。
Lay Abstract Limited reciprocal social interactions are central to the diagnosis of autism. Behavioral intervention programs are effective in improving social and communication skills in children with autism. We are employing mouse models to understand the individual components of behavioral interventions which effectively improve social interactions. BTBR T+tf/J (BTBR) is an inbred strain of mice that exhibits multiple social deficits, unusual vocalizations, and high levels of repetitive behaviors, which are relevant to all three diagnostic symptom categories of autism. C57BL/6J (B6) is an inbred strain of mice that exhibits high sociability and low repetitive behaviors. We reasoned that these mouse strains with low versus high social interactions might be useful for evaluating social peer enrichment as a behavioral intervention during adolescence. Juvenile BTBR and B6 of the same sex were placed in a same home cage and lived together as cagemates until they reached young adulthood. The two control groups were juvenile B6 housed together, and juvenile BTBR housed together. B6 controls that lived with B6 cagemates showed their strain-typical high sociability. BTBR controls that lived with BTBR cagemates showed their strain-typical low sociability. Remarkably, BTBR that shared home cages with B6 showed high sociability as young adults. Peer rearing for either 20 days or 40 days were equally effective. These results from a robust mouse model of autism support the strategy of early behavioral intervention for treating the social domain in autism spectrum disorders, including beneficial interactions with social peers. Scientific Abstract Behavioral therapies are currently the most effective interventions for treating the diagnostic symptoms of autism. We employed a mouse model of autism to evaluate components of behavioral interventions that improve sociability in mice. BTBR T+tf/J (BTBR) is an inbred mouse strain that exhibits prominent behavioral phenotypes with face validity to all three diagnostic symptom categories of autism, including robust and well-replicated deficits in social approach and reciprocal social interactions. To investigate the role of peer interactions in the development of sociability, BTBR juvenile mice were reared in the same home cage with juvenile mice of a highly social inbred strain, C57BL/6J (B6). Subject mice were tested as young adults for sociability and repetitive behaviors. B6 controls reared with B6 showed their strain-typical high sociability. BTBR controls reared with BTBR cagemates showed their strain-typical lack of sociability. In contrast, BTBR reared with B6 as juveniles showed significant sociability as young adults. A 20-day intervention was as effective as a 40-day intervention for improving social approach behavior. High levels of repetitive self-grooming by BTBR were not rescued by peer-rearing with B6, indicating specificity of the intervention to the social domain. These results from a robust mouse model of autism support the interpretation that social enrichment with juvenile peers is a beneficial intervention for improving adult outcome in the social domain. This novel paradigm may prove useful for discovering factors that are essential for effective behavioral treatments, and biological mechanisms underlying effective behavioral interventions.
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