Elevation of EGR1/zif268, a Neural Activity Marker, in the Auditory Cortex of Patients with Schizophrenia and its Animal Model
Elevation of EGR1/zif268, a Neural Activity Marker, in the Auditory Cortex of Patients with Schizophrenia and its Animal Model
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DOI：
10.1007/s11064-022-03599-9
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发表时间：
2022-04-25
影响因子：
4.4
通讯作者：
Nawa, Hiroyuki
中科院分区：
文献类型：
--
作者：
Iwakura, Yuriko;Kawahara-Miki, Ryoka;Nawa, Hiroyuki
包括神经调节蛋白-1在内的表皮生长因子(EGF)家族与精神分裂症的神经病理有关。我们通过给围产期大鼠暴露于EGF建立了精神分裂症大鼠模型，并报告了该模型的听觉病理生理特征，如脉冲前抑制、听觉稳态反应和失配负波与精神分裂症的相关。我们通过监测三种神经活动诱导蛋白：Egr1(Zif268)、c-fos和Arc，评估了该模型中听觉皮质的激活状态，以及精神分裂症患者的激活状态。在活性标志物中，EGF模型组大鼠成年期Egr1蛋白水平显著高于对照组。尽管EGF模型大鼠和对照组大鼠被关在一起，排除了大鼠发声效应的影响，但仍观察到了组内差异。Egr1水平的这些变化被认为是该模型听觉皮质所特有的。Egr1水平在幼年期可检测到，并持续到老年，但在青春期后立即出现峰值，而c-fos和Arc水平在所有年龄段之间几乎无法区分，除Arc在幼年期下降外。精神分裂症患者死后上颞叶皮质中的Egr1水平也有类似的升高。Egr1升高的共性表明，听觉皮质Egr1的升高可能是该动物模型和精神分裂症与幻觉相关的分子特征之一。
The family of epidermal growth factor (EGF) including neuregulin-1 are implicated in the neuropathology of schizophrenia. We established a rat model of schizophrenia by exposing perinatal rats to EGF and reported that the auditory pathophysiological traits of this model such as prepulse inhibition, auditory steady-state response, and mismatch negativity are relevant to those of schizophrenia. We assessed the activation status of the auditory cortex in this model, as well as that in patients with schizophrenia, by monitoring the three neural activity-induced proteins: EGR1 (zif268), c-fos, and Arc. Among the activity markers, protein levels of EGR1 were significantly higher at the adult stage in EGF model rats than those in control rats. The group difference was observed despite an EGF model rat and a control rat being housed together, ruling out the contribution of rat vocalization effects. These changes in EGR1 levels were seen to be specific to the auditory cortex of this model. The increase in EGR1 levels were detectable at the juvenile stage and continued until old ages but displayed a peak immediately after puberty, whereas c-fos and Arc levels were nearly indistinguishable between groups at all ages with an exception of Arc decrease at the juvenile stage. A similar increase in EGR1 levels was observed in the postmortem superior temporal cortex of patients with schizophrenia. The commonality of the EGR1 increase indicates that the EGR1 elevation in the auditory cortex might be one of the molecular signatures of this animal model and schizophrenia associating with hallucination.