Altered cerebellar development in nuclear receptor TAK1/ TR4 null mice is associated with deficits in GLAST(+) glia, alterations in social behavior, motor learning, startle reactivity, and microglia.
Altered cerebellar development in nuclear receptor TAK1/ TR4 null mice is associated with deficits in GLAST(+) glia, alterations in social behavior, motor learning, startle reactivity, and microglia.
复制标题
DOI：
10.1007/s12311-010-0163-z
复制
发表时间：
2010-09
期刊：
影响因子：
3.5
通讯作者：
Jetten, Anton M.
中科院分区：
文献类型：
--
作者：
Kim, Yong-Sik;Harry, G. Jean;Kang, Hong Soon;Goulding, David;Wine, Rob N.;Kissling, Grace E.;Liao, Grace;Jetten, Anton M.
以前，缺乏核孤儿受体TAK 1的表达被发现与延迟小脑颗粒细胞迁移和浦肯野细胞成熟与小叶VI-VII的永久性缺陷有关，这表明TAK 1在小脑发育中的作用。在这项研究中，我们证实了TAK 1缺陷（TAK 1 −/−）小鼠的小脑较小，并表现出小叶VI-VII的破坏。我们扩展了这些研究，并表明在出生后第7天（PND 7），TAK 1 −/−小鼠表现出畸形钙结合蛋白28 K阳性浦肯野细胞单层成熟的延迟。星形胶质细胞特异性谷氨酸转运蛋白（GLAST）在伯格曼纤维和内部颗粒细胞层中表达，在TAK 1 −/−小鼠小脑中的水平显著较低。在PND 21时，TAK 1 −/−小鼠中的高尔基体阳性浦肯野细胞显示出较小的索马（18%）和较短的距离第一分支点（35%）。在PND 21时，在TAK 1 −/−小鼠中未观察到神经元死亡，然而，小脑中存在活化的小胶质细胞，表明细胞早期死亡。小脑中的这些结构缺陷不足以改变运动强度、协调或活动水平;然而，观察到声惊吓反应、前脉冲惊吓抑制和社会互动的缺陷。在光/暗室、开阔场地和家庭笼跑轮中，对新环境的反应受到抑制。TAK 1 −/−小鼠在转轮上表现出一个平台，表明在学习协调运动任务的表现方面存在缺陷。这些数据表明TAK 1是小脑发育和神经发育调节行为的重要转录调节因子。
Previously, deficiency in the expression of the nuclear orphan receptor TAK1 was found to be associated with delayed cerebellar granule cell migration and Purkinje cell maturation with a permanent deficit in foliation of lobules VI–VII suggesting a role for TAK1 in cerebellum development. In this study, we confirm that TAK1-deficient (TAK1−/−) mice have a smaller cerebellum and exhibit a disruption of lobules VI–VII. We extended these studies and show that at postnatal day 7 (PND7), TAK1−/− mice exhibit a delay in monolayer maturation of dysmorphic calbindin 28K-positive Purkinje cells. The astrocyte-specific glutamate transporter (GLAST) was expressed within Bergmann fibers and internal granule cell layer at significantly lower levels in the cerebellum of TAK1−/− mice. At PND21, Golgi-positive Purkinje cells in TAK1−/− mice displayed a smaller soma (18%) and shorter distance to first branch point (35%). Neuronal death was not observed in TAK1−/− mice at PND21, however, activated microglia were present in the cerebellum suggestive of earlier cell death. These structural deficits in the cerebellum were not sufficient to alter motor strength, coordination, or activity levels; however, deficits in acoustic startle response, pre-pulse startle inhibition, and social interactions were observed. Reactions to a novel environment were inhibited in a light/dark chamber, open-field, and home-cage running-wheel. TAK1−/− mice displayed a plateau in performance on the running-wheel suggesting a deficit in learning to coordinate performance on a motor task. These data indicate that TAK1 is an important transcriptional modulator of cerebellar development and neurodevelopmentally-regulated behavior.
登录
查看更多内容
影响因子：
5.3
作者：
Aruga, J;Inoue, T;Mikoshiba, K
通讯作者：
Mikoshiba, K
影响因子：
2.9
作者：
Chen, Yei-Tsung;Collins, Loretta L.;Chang, Chawnshang
通讯作者：
Chang, Chawnshang
DOI：
10.1073/pnas.91.13.6040
发表时间：
1994-06-21
影响因子：
11.1
作者：
CHANG, CS;DASILVA, SL;BURBACH, JPH
通讯作者：
BURBACH, JPH
影响因子：
4.3
作者：
Harry GJ;Kraft AD
通讯作者：
Kraft AD
影响因子：
16.2
作者：
GOLDOWITZ, D
通讯作者：
GOLDOWITZ, D