Rats selectively bred for low levels of play-induced 50 kHz vocalizations as a model for autism spectrum disorders: a role for NMDA receptors.
Rats selectively bred for low levels of play-induced 50 kHz vocalizations as a model for autism spectrum disorders: a role for NMDA receptors.
复制标题
DOI：
10.1016/j.bbr.2013.04.022
复制
发表时间：
2013-08-15
影响因子：
2.7
通讯作者：
Panksepp J
中科院分区：
文献类型：
--
作者：
Burgdorf J;Moskal JR;Brudzynski SM;Panksepp J
早期儿童孤独症的特征是社交方法和游戏行为，社会情感相关性和沟通/言语异常以及重复行为的缺陷。自闭症的这些核心神经心理学特征可以在实验室大鼠中建模，结果可能对药物发现和治疗开发有用。我们回顾的数据表明，大鼠选择性饲养的低利率的游戏相关的亲社会超声发声（USVs）可以用来模拟自闭症的社会缺陷症状。与非选择性繁殖的随机线动物相比，低线动物与同种动物的社会接触时间较少，表现出较低的游戏诱导亲社会USV的比率，并且表现出非频率调制（即单调）超声发声的比例增加。低线动物的基因表达模式显示自闭症相关基因的显著富集，并且NMDA受体家族被鉴定为重要的枢纽。用NMDAR功能性甘氨酸位点部分激动剂GLYX-13治疗低线动物，挽救了玩耍诱导的亲社会50 kHz USV的缺陷，并减少了单调的USV。由于NMDA受体与自闭症症状的发生有关，因此GLYX-13可能在自闭症的治疗中具有治疗价值。
Early childhood autism is characterized by deficits in social approach and play behaviors, socio-emotional relatedness, and communication/speech abnormalities, as well as repetitive behaviors. These core neuropsychological features of autism can be modeled in laboratory rats, and the results may be useful for drug discovery and therapeutic development. We review data that show that rats selectively bred for low rates of play-related pro-social ultrasonic vocalizations (USVs) can be used to model social deficit symptoms of autism. Low-line animals engage in less social contact time with conspecifics, show lower rates of play induced pro-social USVs, and show an increased proportion of non-frequency modulated (i.e. monotonous) ultrasonic vocalizations compared to non-selectively bred random-line animals. Gene expression patterns in the low-line animals show significant enrichment in autism-associated genes, and the NMDA receptor family was identified as a significant hub. Treatment of low-line animals with the NMDAR functional glycine site partial agonist, GLYX-13, rescued the deficits in play-induced pro-social 50-kHz USVs and reduced monotonous USVs. Since the NMDA receptor has been implicated in the genesis of autistic symptoms, it is possible that GLYX-13 may be of therapeutic value in the treatment of autism.