Amygdala DCX and blood Cdk14 are implicated as cross-species indicators of individual differences in fear, extinction, and resilience to trauma exposure.
Amygdala DCX and blood Cdk14 are implicated as cross-species indicators of individual differences in fear, extinction, and resilience to trauma exposure.
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DOI：
10.1038/s41380-021-01353-1
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发表时间：
2022-03
影响因子：
11
通讯作者：
Ressler, K. J.
中科院分区：
文献类型：
--
作者：
Maheu, M. E.;Sharma, S.;King, G.;Maddox, S. A.;Wingo, A.;Lori, A.;Michopoulos, V.;Richardson, R.;Ressler, K. J.
双皮质素 (DCX) 长期以来一直与神经发生有关，并被用作神经发生的标记物，但对其在非神经发生大脑区域（包括杏仁核）中的功能知之甚少。本研究首先试图在啮齿动物中探索恐惧学习和消退是否调节杏仁核 DCX 表达，其次评估外周 DCX 作为啮齿动物和人类创伤反应的预测生物标志物的实用性。研究发现巴甫洛夫条件反射会在 24 小时后改变小鼠的 DCX 蛋白水平，从而导致更高的 DCX 表达，这与检查恐惧获得和消失的范式中的学习增强相关（p < 0.001）。反过来，这与随后的恐惧表达测试中冻结的差异有关，并且 DCX 和恐惧消退之间的相同关系在大鼠中也得到了复制 (p < 0.001)，杏仁核 DCX 水平越高，恐惧消退越快。杏仁核和小鼠血液的 RNAseq 鉴定出 388 个与 DCX 相关的杏仁核基因 (q < 0.001)，并且基因本体分析显示这些基因在神经发育过程中显着过度表达。在血液中，DCX 相关基因包括 Wnt 信号分子 Cdk14，人们发现它可以预测恐惧获得 (p < 0.05) 和短暂消退过程 (p < 0.001) 期间的冻结。测试后立即在血液中测得的高 Cdk14 也与恐惧表达测试期间较少的僵硬有关（p < 0.01）。最后，在人类中，创伤后不久采集的血液中 Cdk14 的表达被发现可以预测男性创伤后长达一年的恢复能力 (p < 0.0001)。这些数据表明杏仁核 DCX 与恐惧学习有关，并表明 Cdk14 可以作为创伤反应的预测生物标志物。
Doublecortin (DCX) has long been implicated in, and employed as a marker for, neurogenesis, yet little is known about its function in non-neurogenic brain regions, including the amygdala. This study sought first to explore, in rodents, whether fear learning and extinction modulate amygdala DCX expression and, second, to assess the utility of peripheral DCX correlates as predictive biomarkers of trauma response in rodents and humans. Pavlovian conditioning was found to alter DCX protein levels in mice 24 hours later, resulting in higher DCX expression associated with enhanced learning in paradigms examining both the acquisition and extinction of fear (p < 0.001). This, in turn, is associated with differences in freezing on subsequent fear expression tests, and the same relationship between DCX and fear extinction was replicated in rats (p < 0.001), with higher amygdala DCX levels associated with more rapid extinction of fear. RNAseq of amygdala and blood from mice identified 388 amygdala genes that correlated with DCX (q < 0.001) and which gene ontology analyses revealed were significantly over-represented for neurodevelopmental processes. In blood, DCX-correlated genes included the Wnt signaling molecule Cdk14 which was found to predict freezing during both fear acquisition (p < 0.05) and brief extinction protocols (p < 0.001). High Cdk14 measured in blood immediately after testing was also associated with less freezing during fear expression testing (p < 0.01). Finally, in humans, Cdk14 expression in blood taken shortly after trauma was found to predict resilience in males for up to a year post-trauma (p < 0.0001). These data implicate amygdala DCX in fear learning and suggest that Cdk14 may serve as a predictive biomarker of trauma response.
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影响因子：
3.7
作者：
Mina E;van Roon-Mom W;Hettne K;van Zwet E;Goeman J;Neri C;A C 't Hoen P;Mons B;Roos M
通讯作者：
Roos M
β-连环蛋白是记忆巩固所必需的。
影响因子：
25
作者：
Maguschak, Kimberly A.;Ressler, Kerry J.
通讯作者：
Ressler, Kerry J.
影响因子：
7.4
作者：
Connor, KM;Davidson, JRT
通讯作者：
Davidson, JRT
影响因子：
4.8
作者：
Ayanlaja AA;Xiong Y;Gao Y;Ji G;Tang C;Abdikani Abdullah Z;Gao D
通讯作者：
Gao D
影响因子：
2.8
作者：
Bourgeois, F.;Messeant, J.;Legay, C.
通讯作者：
Legay, C.