Stress-induced hippocampus Npas4 mRNA expression relates to specific psychophysiological patterns of stress response

Stress-induced hippocampus Npas4 mRNA expression relates to specific psychophysiological patterns of stress response
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DOI:
10.1016/j.brainres.2017.11.024
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发表时间:
2018-01-15
期刊:
影响因子:
2.9
通讯作者:
Canini, Frederic
Canini, Frederic
中科院分区:
医学3区
文献类型:
--
作者:
Drouet, Jean-Baptiste;Peinnequin, Andre;Canini, Frederic

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神经元PAS结构域蛋白4(NeuronalPer-Arnt-Sim,Npas 4)是一种重要的神经元蛋白,参与GABA突触的调节和神经营养性的增强。由于GABA和神经营养性与应激反应有关,Npas 4缺陷的啮齿动物表现出行为改变,因此设计了一项大鼠研究,以验证应激诱导的自发海马Npas 4 mRNA表达是否与应激反应的特定模式相关。将大鼠暴露于三种应激源水平之一:无应激(CTL,n = 15),暴露于足电击装置(Sham,S,n = 40)和足电击(F,n = 80)。应激暴露后,S和F大鼠在活动笼中进行测试,随后在处死前在高架十字迷宫(高架十字迷宫)中进行测试。使用聚类分析,已经分配到应激水平的动物也根据其Npas 4 mRNA水平分为2个亚组。在S和F组中鉴定了低(L)和高(H)Npas 4表达亚组,CTL组与Npas 4水平无关。通过胁迫(S和F)与Npas 4水平(L和H)之间的交互作用来研究Npas 4效应。H和L大鼠的生物应激反应相似,只是H大鼠的血液皮质酮略低。H组大鼠在活动测定笼中更活跃,在活动测定笼中表现出更高的探索水平。通过c-fos、Egri和Arc mRNA水平评估,他们也表现出更高的海马激活。因此,高Npas 4表达有利于应激管理。(C)2017爱思唯尔B. V.保留所有权利。
Neuronal Per-Arnt-Sim (PAS) domain protein 4 (Npas4) is a key protein that intervenes in GABA synapse scaling and neurotrophicity enhancing. Since GABA and neurotrophicity are implicated in stress response and Npas4-deficient rodents exhibit behavioral alterations, an investigation was designed in rats to verify whether stress-induced spontaneous hippocampus Npas4 mRNA expression would be associated with specific patterns of stress response. The rats were exposed to one of three stressor levels: no stress (CTL, n = 15), exposure to a footshock apparatus (Sham, S, n = 40) and footshock (F, n = 80). After stress exposure the S and F rats were tested in an activity cage, and subsequently in an elevated plus maze (EPM), just prior to the sacrifice. Using cluster analysis, the animals already assigned to a stress level were also distributed into 2 subgroups depending on their Npas4 mRNA levels. The low (L) and high (H) Npas4 expression subgroups were identified in the S and F groups, the CTL group being independent of the Npas4 levels. The Npas4 effect was studied through the interaction between stress (S and F) and Npas4 level (L and H). The biological stress response was similar in H and L rats, except blood corticosterone that was slightly lower in the H rats. The H rats were more active in the actimetry cage and presented higher levels of exploration in the EPM. They also exhibited higher hippocampus activation, as assessed by the c-fos, Egri and Arc mRNA levels. Therefore high Npas4 expression favors stress management. (C) 2017 Elsevier B.V. All rights reserved.