High-Frequency Stimulation at the Subthalamic Nucleus Suppresses Excessive Self-Grooming in Autism-Like Mouse Models
High-Frequency Stimulation at the Subthalamic Nucleus Suppresses Excessive Self-Grooming in Autism-Like Mouse Models
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DOI：
10.1038/npp.2015.350
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发表时间：
2016-06-01
影响因子：
7.6
通讯作者：
Reti, Irving M.
中科院分区：
文献类型：
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作者：
Chang, Andrew D.;Berges, Victoria A.;Reti, Irving M.
大约四分之一的自闭症谱系障碍（ASD）患者表现出自我伤害行为（SIB），从头部撞击到自我导向的咬和拳击。有时，这些行为是极端的，对药理学和行为疗法没有反应。我们发现电休克治疗（ECT）可以产生改变生活的结果，对SIB频率的抑制超过90%。然而，这些患者通常需要频繁的维持ECT（mECT），每5天一次，以维持治疗。急性期病情有所改善。在某些情况下，这种频繁的mECT早在儿童时期就开始了，其长期后果尚不清楚。因此，需要用于这些患者的替代形式的慢性刺激。为了探索深部脑刺激（DBS）治疗一些ASD患者中出现的顽固性SIB的可行性，我们使用了两种遗传上不同的小鼠模型，即Viaat-Mecp（2-ly）和Shank 3B（-/-）线，并通过在丘脑底核（STN-HFS）植入电极进行高频刺激（HFS）。我们发现，STN-HFS显着抑制过度的自我梳理在两个遗传线。当刺激开启时，抑制发生急性，并且在HFS停止后持续数天。这种影响不能解释为自发活动的变化，这是不受STN-HFS。同样，STN-HFS也不能纠正社会交往缺陷。我们的数据显示，STN-HFS在两种自闭症样小鼠模型中抑制了过度的自我修饰，提高了DBS可能用于治疗与ASD相关的顽固性SIB的可能性。需要进一步的研究来探索STN-HFS参与的电路以及其他潜在的刺激部位。这样的研究也可能产生关于通路的线索，这些通路可以通过非侵入性刺激技术来调节。
Approximately one quarter of individuals with an autism spectrum disorder (ASD) display self-injurious behavior (SIB) ranging from head banging to self-directed biting and punching. Sometimes, these behaviors are extreme and unresponsive to pharmacological and behavioral therapies. We have found electroconvulsive therapy (ECT) can produce life-changing results, with more than 90% suppression of SIB frequency. However, these patients typically require frequent maintenance ECT (mECT), as often as every 5 days, to sustain the. improvement gained during the acute course. Long-term consequences of such frequent mECT started as early as childhood in some cases are unknown. Accordingly, there is a need for alternative forms of chronic stimulation for these patients. To explore the feasibility of deep brain stimulation (DBS) for intractable SIB seen in some patients with an ASD, we utilized two genetically distinct mouse models demonstrating excessive self-grooming, namely the Viaat-Mecp(2-ly) and Shank3B(-/-) lines, and administered high-frequency stimulation (HFS) via implanted electrodes at the subthalamic nucleus (STN-HFS). We found that STN-HFS significantly suppressed excessive self grooming in both genetic lines. Suppression occurs both acutely when stimulation is switched on, and persists for several days after HFS is stopped. This effect was not explained by a change in locomotor activity, which was unaffected by STN-HFS. Likewise, social interaction deficits were not corrected by STN-HFS. Our data show STN-HFS suppresses excessive self-grooming in two autism-like mouse models, raising the possibility DBS might be used to treat intractable SIB associated with ASDs. Further studies are required to explore the circuitry engaged by STN-HFS, as well as other potential stimulation sites. Such studies might also yield clues about pathways, which could be modulated by non-invasive stimulatory techniques.