Endogenous truncated TrkB.T1 receptor regulates neuronal complexity and TrkB kinase receptor function in vivo.
Endogenous truncated TrkB.T1 receptor regulates neuronal complexity and TrkB kinase receptor function in vivo.
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DOI：
10.1523/jneurosci.5060-08.2009
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发表时间：
2009-01-21
期刊：
影响因子：
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通讯作者：
Tessarollo L
中科院分区：
文献类型：
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作者：
Carim-Todd L;Bath KG;Fulgenzi G;Yanpallewar S;Jing D;Barrick CA;Becker J;Buckley H;Dorsey SG;Lee FS;Tessarollo L
病理或体外过表达截断的TrkB。T1受体通过全长TrkB （TrkB. fl）酪氨酸激酶受体抑制信号传导。然而，到目前为止，内源性TrkB的作用。T1还是未知的。通过研究缺乏截断TrkB的小鼠。T1亚型，但保持TrkB的正常时空表达。我们分析了TrkB。T1特异性生理功能及其对体内内源性TrkB激酶信号传导的影响。我们发现TrkB。T1缺陷小鼠发育正常，但焦虑增加与杏仁核基底外侧神经元的神经突长度和复杂性的形态学异常有关。然而，在海马依赖记忆任务中未检测到行为异常，这与缺乏明显的海马形态缺陷或基础突触传递和长期增强（LTP）的改变有关。在体内，通过去除一个BDNF等位基因而减少的TrkB信号传导可以被TrkB部分挽救。T1缺失，这是通过改善与BDNF单倍不足相关的攻击性增强和体重增加而揭示的。我们的结果表明，在生理水平上，TrkB。T1受体是TrkB的重要调节因子。体内FL信号。此外,TrkB。T1选择性地影响某些神经元群的树突复杂性。
Pathological or in vitro over expression of the truncated TrkB.T1 receptor inhibits signaling through the full-length TrkB (TrkB.FL) tyrosine kinase receptor. However, to date, the role of endogenous TrkB.T1 is still unknown. By studying mice lacking the truncated TrkB.T1 isoform but retaining normal spatio-temporal expression of TrkB.FL we have analyzed TrkB.T1 specific physiological functions and its effect on endogenous TrkB kinase signaling in vivo. We found that TrkB.T1 deficient mice develop normally but show increased anxiety in association with morphological abnormalities in the length and complexity of neurites of neurons in the basolateral amygdala. However, no behavioral abnormalities were detected in hippocampal-dependent memory tasks, which correlated with lack of any obvious hippocampal morphological deficits or alterations in basal synaptic transmission and Long-Term Potentiation (LTP). In vivo reduction of TrkB signaling by removal of one BDNF allele could be partially rescued by TrkB.T1 deletion, which was revealed by an amelioration of the enhanced aggression and weight gain associated to BDNF haploinsufficiency. Our results suggest that at the physiological level, TrkB.T1 receptors are important regulators of TrkB.FL signaling in vivo. Moreover, TrkB.T1 selectively affects dendrite complexity of certain neuronal populations.