Trib3 is developmentally and nutritionally regulated in the brain but is dispensable for spatial memory, fear conditioning and sensing of amino acid-imbalanced diet.
Trib3 is developmentally and nutritionally regulated in the brain but is dispensable for spatial memory, fear conditioning and sensing of amino acid-imbalanced diet.
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DOI：
10.1371/journal.pone.0094691
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Örd T
中科院分区：
文献类型：
--
作者：
Örd T;Innos J;Lilleväli K;Tekko T;Sütt S;Örd D;Kõks S;Vasar E;Örd T
Tribbles同系物3（TRIB 3）是哺乳动物假激酶，其在神经元细胞培养物中响应于细胞死亡诱导应激（包括神经营养因子剥夺）而被诱导。TRIB3是转录激活因子4（ATF4）的抑制剂，ATF4是真核翻译起始因子2α（eIF2α）磷酸化途径中的中心转录调节因子，其参与细胞应激反应和行为过程。在这篇文章中，我们研究了Trib3在小鼠脑中的表达，表征了Trib3基因敲除小鼠的脑形态，并研究了Trib3缺陷是否会改变eIF2α依赖的认知能力。我们的数据表明，亮氨酸缺乏饮食的消费诱导Trib3表达在前梨状皮质，负责检测必需氨基酸摄入量不平衡的大脑区域。然而，Trib3基因敲除小鼠和野生型小鼠对无亮氨酸饮食的厌恶反应没有差异。Trib3缺失也不影响长期空间记忆和Morris水迷宫中的反向学习以及听觉或背景恐惧条件反射。在胚胎发育过程中，Trib3在大脑中的表达增加，并持续到出生后早期。缺乏Trib3的小鼠的神经解剖学特征显示侧脑室扩大。因此，尽管Trib3的缺失不会改变包括海马、杏仁核和前梨状皮质在内的几个脑区的eIF2α通路依赖性认知功能，但Trib3可能在其他中枢神经系统过程和分子通路中发挥作用。
Tribbles homolog 3 (TRIB3) is a mammalian pseudokinase that is induced in neuronal cell cultures in response to cell death-inducing stresses, including neurotrophic factor deprivation. TRIB3 is an inhibitor of activating transcription factor 4 (ATF4), the central transcriptional regulator in the eukaryotic translation initiation factor 2α (eIF2α) phosphorylation pathway that is involved in the cellular stress response and behavioral processes. In this article, we study the expression of Trib3 in the mouse brain, characterize the brain morphology of mice with a genetic ablation of Trib3 and investigate whether Trib3 deficiency alters eIF2α-dependent cognitive abilities. Our data show that the consumption of a leucine-deficient diet induces Trib3 expression in the anterior piriform cortex, the brain region responsible for detecting essential amino acid intake imbalance. However, the aversive response to leucine-devoid diet does not differ in Trib3 knockout and wild type mice. Trib3 deletion also does not affect long-term spatial memory and reversal learning in the Morris water maze and auditory or contextual fear conditioning. During embryonic development, Trib3 expression increases in the brain and persists in the early postnatal stadium. Neuroanatomical characterization of mice lacking Trib3 revealed enlarged lateral ventricles. Thus, although the absence of Trib3 does not alter the eIF2α pathway-dependent cognitive functions of several areas of the brain, including the hippocampus, amygdala and anterior piriform cortex, Trib3 may serve a role in other central nervous system processes and molecular pathways.
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影响因子：
3.7
作者：
Juknat A;Pietr M;Kozela E;Rimmerman N;Levy R;Gao F;Coppola G;Geschwind D;Vogel Z
通讯作者：
Vogel Z
影响因子：
29
作者：
Maurin, AC;Jousse, C;Fafournoux, P
通讯作者：
Fafournoux, P
影响因子：
2.8
作者：
Allen, JS;Damasio, H;Grabowski, TJ
通讯作者：
Grabowski, TJ
影响因子：
64.8
作者：
Costa-Mattioli, M;Gobert, D;Sonenberg, N
通讯作者：
Sonenberg, N
影响因子：
4.2
作者：
Koehnle, TJ;Russell, MC;Gietzen, DW
通讯作者：
Gietzen, DW