EGR3 Immediate Early Gene and the Brain-Derived Neurotrophic Factor in Bipolar Disorder.
EGR3 Immediate Early Gene and the Brain-Derived Neurotrophic Factor in Bipolar Disorder.
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DOI：
10.3389/fnbeh.2018.00015
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发表时间：
2018
影响因子：
3
通讯作者：
Klamt F
中科院分区：
文献类型：
--
作者：
Pfaffenseller B;Kapczinski F;Gallitano AL;Klamt F
双相情感障碍（BD）是一种严重的精神疾病，具有一致的遗传影响，涉及许多基因和环境因素之间的复杂相互作用。立即早期基因（IEG）在大脑中响应环境刺激（例如压力）而被激活。将环境刺激转化为大脑长期变化的可能性导致人们对这些基因影响精神疾病风险的潜在作用越来越感兴趣。我们最近的研究发现，使用网络为基础的方法表明，早期生长反应基因3（EGR3）的调节单位的IEGs家族在死后BD患者的前额叶皮层强烈抑制。作为一个中心转录因子，EGR3调节一系列靶基因，介导关键的神经生物学过程，如突触可塑性，记忆和认知。考虑到EGR3的表达是由脑源性神经营养因子（BDNF）诱导的，BDNF一直与BD病理生理学相关，我们建议BDNF和EGR3之间的联系及其在BD中的潜在作用。来自我们小组和其他人的越来越多的数据表明，外周BDNF水平在情绪发作和疾病进展期间降低。在这同一静脉中，BDNF已被提出作为与BD相关的受损细胞弹性中的重要生长因子。考虑到EGR3调节神经营养因子受体p75NTR的表达，也可能间接诱导BDNF的表达，在这里，我们提出了一个前馈基因调控网络，涉及EGR3和BDNF及其在BD中的潜在作用。
Bipolar disorder (BD) is a severe psychiatric illness with a consistent genetic influence, involving complex interactions between numerous genes and environmental factors. Immediate early genes (IEGs) are activated in the brain in response to environmental stimuli, such as stress. The potential to translate environmental stimuli into long-term changes in brain has led to increased interest in a potential role for these genes influencing risk for psychiatric disorders. Our recent finding using network-based approach has shown that the regulatory unit of early growth response gene 3 (EGR3) of IEGs family was robustly repressed in postmortem prefrontal cortex of BD patients. As a central transcription factor, EGR3 regulates an array of target genes that mediate critical neurobiological processes such as synaptic plasticity, memory and cognition. Considering that EGR3 expression is induced by brain-derived neurotrophic factor (BDNF) that has been consistently related to BD pathophysiology, we suggest a link between BDNF and EGR3 and their potential role in BD. A growing body of data from our group and others has shown that peripheral BDNF levels are reduced during mood episodes and also with illness progression. In this same vein, BDNF has been proposed as an important growth factor in the impaired cellular resilience related to BD. Taken together with the fact that EGR3 regulates the expression of the neurotrophin receptor p75NTR and may also indirectly induce BDNF expression, here we propose a feed-forward gene regulatory network involving EGR3 and BDNF and its potential role in BD.
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