Psychiatry Unit, Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy.
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT, USA.
CNS Neurosci Ther. 2018 Aug;24(8):703-711. doi: 10.1111/cns.12789. Epub 2018 Jan 3.
The transgenic D1CT-7 mouse is one of the best-characterized animal models of Tourette's syndrome (TS), exhibiting spontaneous tic-like Head-Body Twitches (HBT) and deficits in sensorimotor gating. This study is aimed at evaluating the behavioral dynamics of these mutants and their potential relevance to TS.
The behavior of D1CT-7 and Wild Type littermates was firstly assessed by considering frequencies and durations. To detect recurrent real-time behavioral sequences, the multivariate T-pattern analysis was employed. Analyses of transition probabilities among behaviors further provided an overall picture of the behavioral dynamics.
T-patterns and transition matrices revealed in D1CT-7 mice a clear-cut hyperactivity compared to controls, with a lower behavioral organization and a marked shift from cautious sniffing toward locomotion. Moreover, the behavioral patterns of the transgenic mice were pervasively disturbed by intrusive tic-like HBT leading to a marked fragmentation of the behavior. Novel exposure to open field provoked a transient inhibitory control over the disrupting phenotype.
The results of this study show that the D1CT-7 mouse model is subjected to a behavioral fragmentation, with repercussions going beyond the simple tic-like phenomenon. These phenotypes are strikingly akin to behavioral problems observed in patients with TS and further validate the power of this model in summarizing pivotal behavioral aspects of TS.
转基因 D1CT-7 小鼠是抽动秽语综合征(TS)最具特征性的动物模型之一,表现出自发性抽搐样头身抽搐(HBT)和感觉运动门控缺陷。本研究旨在评估这些突变体的行为动态及其与 TS 的潜在相关性。
首先通过考虑频率和持续时间来评估 D1CT-7 和野生型同窝仔鼠的行为。为了检测实时行为序列的重复,采用了多元 T 模式分析。对行为之间的转移概率的分析进一步提供了行为动态的整体情况。
T 模式和转移矩阵显示,与对照组相比,D1CT-7 小鼠表现出明显的过度活跃,行为组织性降低,从谨慎嗅探向运动的明显转变。此外,转基因小鼠的行为模式被侵入性抽搐样 HBT 严重扰乱,导致行为明显碎片化。新暴露于开阔场会暂时抑制破坏表型。
本研究结果表明,D1CT-7 小鼠模型存在行为碎片化,其影响超出了单纯的抽搐样现象。这些表型与 TS 患者观察到的行为问题非常相似,进一步验证了该模型在总结 TS 的关键行为方面的强大功能。