miR-218: A Stress-Responsive Epigenetic Modifier.
miR-218: A Stress-Responsive Epigenetic Modifier.
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DOI：
10.3390/ncrna8040055
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发表时间：
2022-07-21
期刊：
影响因子：
4.3
通讯作者：
Dwivedi, Yogesh
中科院分区：
文献类型：
--
作者：
Schell, Grant;Roy, Bhaskar;Prall, Kevin;Dwivedi, Yogesh
了解 microRNA (miRNA) 的表观遗传作用是神经精神病学领域及其潜在病理生理学的关键进展。 miRNA 表达异常通常被视为许多与压力相关的精神疾病（包括重度抑郁症 (MDD)）发病机制的关键。组学生物学的最新进展进一步促进了这种理解，并扩大了 miRNA 在连接多种分子通路中的作用，这些分子通路本质上与健康大脑的压力适应性有关。研究强调了许多此类 miRNA 在引起大脑应激轴适应不良变化中的作用。其中一种 miRNA 是 miR-218，它被认为是增加应激敏感性的关键候选者。 miR-218 在整个大脑中表达，特别是在海马体和前额皮质 (PFC) 中。正如青少年和成年动物模型所见，它在整个生命阶段以不同水平表达。到目前为止，已经对人类受试者进行了少量研究，以了解其在大脑回路中与压力相关的异常中的作用。然而，包括动物和细胞培养模型在内的多项研究已被用来了解 miR-218 对应激反应和下丘脑-垂体-肾上腺 (HPA) 轴功能的影响。迄今为止，已经发现该 miRNA 的表达变化可以调节信号通路，例如糖皮质激素信号、血清素信号和谷氨酸信号。最近，miR-218 的发育作用引起了人们的兴趣，因为它从青春期到成年的表达不断增加，并且靶向 Netrin-1/DCC 信号通路。由于 miR-218 表达影响神经元发育和可塑性，因此预计在发育过程中 miR-218 表达水平的变化可能会对这一过程产生负面影响，并使个体在成年后对压力敏感。在这篇综述中，我们描述了 miR-218 在压力诱发的神经精神疾病中的作用，重点是压力相关疾病。
Understanding the epigenetic role of microRNAs (miRNAs) has been a critical development in the field of neuropsychiatry and in understanding their underlying pathophysiology. Abnormalities in miRNA expression are often seen as key to the pathogenesis of many stress-associated mental disorders, including major depressive disorder (MDD). Recent advances in omics biology have further contributed to this understanding and expanded the role of miRNAs in networking a diverse array of molecular pathways, which are essentially related to the stress adaptivity of a healthy brain. Studies have highlighted the role of many such miRNAs in causing maladaptive changes in the brain’s stress axis. One such miRNA is miR-218, which is debated as a critical candidate for increased stress susceptibility. miR-218 is expressed throughout the brain, notably in the hippocampus and prefrontal cortex (PFC). It is expressed at various levels through life stages, as seen by adolescent and adult animal models. Until now, a minimal number of studies have been conducted on human subjects to understand its role in stress-related abnormalities in brain circuits. However, several studies, including animal and cell-culture models, have been used to understand the impact of miR-218 on stress response and hypothalamic-pituitary-adrenal (HPA) axis function. So far, expression changes in this miRNA have been found to regulate signaling pathways such as glucocorticoid signaling, serotonergic signaling, and glutamatergic signaling. Recently, the developmental role of miR-218 has generated interest, given its increasing expression from adolescence to adulthood and targeting the Netrin-1/DCC signaling pathway. Since miR-218 expression affects neuronal development and plasticity, it is expected that a change in miR-218 expression levels over the course of development may negatively impact the process and make individuals stress-susceptible in adulthood. In this review, we describe the role of miR-218 in stress-induced neuropsychiatric conditions with an emphasis on stress-related disorders.