Repetitive behavior and increased activity in mice with Purkinje cell loss: a model for understanding the role of cerebellar pathology in autism.
Repetitive behavior and increased activity in mice with Purkinje cell loss: a model for understanding the role of cerebellar pathology in autism.
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DOI：
10.1111/j.1460-9568.2009.07073.x
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发表时间：
2010-02
期刊：
影响因子：
--
通讯作者：
Mittleman G
中科院分区：
文献类型：
--
作者：
Martin LA;Goldowitz D;Mittleman G
重复行为和多动症是发育障碍的常见特征，包括自闭症。小脑的神经病理学也经常发生在自闭症和其他发育障碍中。最近的研究表明，小脑病理可能在重复和多动行为的产生中起着因果作用。在这项研究中，我们研究了小脑病理和这些行为之间的关系，在小鼠模型的浦肯野细胞损失。具体而言，我们在Lc/+突变胚胎和+/+胚胎之间制备了聚集嵌合体。Lc/+小鼠由于细胞内在功能获得性突变而在出生后失去100%的浦肯野细胞。通过我们的组织学检查，我们证明了Lc/+ Participate +/+嵌合小鼠具有范围从零到正常数量的浦肯野细胞。我们对这些嵌合体小脑的分析证实了以前对浦肯野细胞谱系的研究。旷场活动和洞板探索测试的结果表明，浦肯野细胞数量和活动措施之间呈负相关，并解释性鼻戳。此外，在进行比操作范例中，我们发现Lc/+小鼠的血压显著低于+/+对照组，这导致该组的断点显著降低。与此相反，嵌合体小鼠β-压显着高于对照组，这种重复的β-压行为显着和总浦肯野细胞数呈负相关。虽然Lc/+小鼠的表现可能与其运动缺陷有关，但浦肯野细胞数量与重复性压迫行为以及旷场活动测量之间的显著关系为小脑病理学在嵌合小鼠中产生重复行为和增加活动中的作用提供了支持。
Repetitive behaviors and hyperactivity are common features of developmental disorders, including autism. Neuropathology of the cerebellum is also a frequent occurrence in autism and other developmental disorders. Recent studies have indicated that cerebellar pathology may play a causal role in the generation of repetitive and hyperactive behaviors. In this study, we examined the relationship between cerebellar pathology and these behaviors in a mouse model of Purkinje cell loss. Specifically, we made aggregation chimeras between Lc/+ mutant embryos and +/+ embryos. Lc/+ mice lose 100% of their Purkinje cells postnatally due to a cell-intrinsic gain-of-function mutation. Through our histological examination, we demonstrated that Lc/+↔+/+ chimeric mice have Purkinje cells ranging from zero to normal numbers. Our analysis of these chimeric cerebella confirmed previous studies on Purkinje cell lineage. The results of both open-field activity and hole-board exploration testing indicated negative relationships between Purkinje cell number and measures of activity and investigatory nose-poking. Additionally, in a progressive-ratio operant paradigm, we found that Lc/+ mice lever-pressed significantly less than +/+ controls, which led to significantly lower breakpoints in this group. In contrast, chimeric mice lever-pressed significantly more than controls and this repetitive lever-pressing behavior was significantly and negatively correlated with total Purkinje cell numbers. Although the performance of Lc/+ mice is probably related to their motor deficits, the significant relationships between Purkinje cell number and repetitive lever-pressing behavior as well as open-field activity measures provide support for a role of cerebellar pathology in generating repetitive behavior and increased activity in chimeric mice.
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影响因子：
4.5
作者：
DAVIS, HN;WATKINS, GM;RUBIA, FJ
通讯作者：
RUBIA, FJ
DOI：
10.1053/ejpn.2002.0582
发表时间：
2002-01-01
期刊：
European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society
影响因子：
--
作者：
Hottinger-Blanc, Pauline M Z;Ziegler, Anne-Lise;Deonna, Thierry
通讯作者：
Deonna, Thierry
影响因子：
--
作者：
ABERCROMBIE, M
通讯作者：
ABERCROMBIE, M
影响因子：
3.4
作者：
Hawkes, R;Faulkner-Jones, B;Tan, SS
通讯作者：
Tan, SS
DOI：
10.1098/rstb.1979.0055
发表时间：
1979-01-01
影响因子：
6.3
作者：
CADDY, KWT;BISCOE, TJ
通讯作者：
BISCOE, TJ