Patterns of cilia gene dysregulations in major psychiatric disorders.
Patterns of cilia gene dysregulations in major psychiatric disorders.
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DOI：
10.1016/j.pnpbp.2021.110255
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发表时间：
2021-07-13
影响因子：
5.6
通讯作者：
Alachkar, Amal
中科院分区：
文献类型：
--
作者：
Alhassen, Wedad;Chen, Siwei;Vawter, Marquis;Robbins, Brianna Kay;Nguyen, Henry;Myint, Thant Nyi;Saito, Yumiko;Schulmann, Anton;Nauli, Surya M.;Civelli, Olivier;Baldi, Pierre;Alachkar, Amal
初级纤毛充当细胞的“天线”，用于检测和转导外部刺激，在细胞信号传导和通讯中发挥着关键作用。绝大多数与纤毛病存在因果关联的纤毛基因，也与神经功能缺陷（如认知缺陷）相关。然而，纤毛功能障碍在精神疾病发病机制中的作用尚未得到研究。我们的目标是确定四种主要精神疾病（精神分裂症（SCZ）、自闭症谱系障碍（ASD）、双相情感障碍（BP）和重度抑郁症（MDD））中纤毛基因的失调模式。为此，我们从规模最大且最新的公开数据库中获取了差异表达基因（DEGs）。我们发现，在精神分裂症、自闭症谱系障碍、双相情感障碍和重度抑郁症中，分别有42%、24%、17%和15%的脑纤毛基因存在显著差异表达。有几个基因在不同疾病间存在重叠，这表明典型的纤毛信号通路功能障碍决定了对不止一种精神疾病的易感性，或者可能在一定程度上构成了这些疾病病理生理学的基础。我们的研究表明，在这四种精神疾病中，几乎所有纤毛亚结构和功能区室的蛋白质编码基因都出现了失调。值得注意的是，在精神分裂症中，75%的纤毛G蛋白偶联受体（GPCRs）基因和50%的过渡区蛋白基因存在差异表达。
本研究首次揭示了纤毛与主要精神疾病之间的关联，是朝着理解纤毛成分在这些疾病病理生理过程中所起作用迈出的第一步，这可能会为这些疾病带来新的治疗靶点。
Primary cilia function as cells’ antennas to detect and transduce external stimuli and play crucial roles in cell signaling and communication. The vast majority of cilia genes that are causally linked with ciliopathies are also associated with neurological deficits, such as cognitive deficits. Yet, the roles of cilia dysfunctions in the pathogenesis of psychiatric disorders have not been studied. Our aim is to identify patterns of cilia gene dysregulation in the four major psychiatric disorders: schizophrenia (SCZ), autism spectrum disorder (ASD), bipolar disorder (BP), and major depressive disorder (MDD). For this purpose, we acquired differentially expressed genes (DEGs) from the largest and most recent publicly available databases. We found that 42%, 24%, 17%, and 15% of brain cilia genes were significantly differentially expressed in SCZ, ASD, BP, and MDD, respectively. Several genes exhibited cross-disorder overlap, suggesting that typical cilia signaling pathways’ dysfunctions determine susceptibility to more than one psychiatric disorder or may partially underlie their pathophysiology. Our study revealed that genes encoding proteins of almost all sub-cilia structural and functional compartments were dysregulated in the four psychiatric disorders. Strikingly, the genes of 75% of cilia GPCRs and 50% of the transition zone proteins were differentially expressed in SCZ. The present study is the first to draw associations between cilia and major psychiatric disorders, and is the first step toward understanding the role that cilia components play in their pathophysiological processes, which may lead to novel therapeutic targets for these disorders.
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自闭症谱系障碍（ASD）、精神分裂症和双相情感障碍中全转录组异构体水平失调
影响因子：
56.9
作者：
Gandal, Michael J.;Zhang, Pan;Geschwind, Daniel H.
通讯作者：
Geschwind, Daniel H.
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影响因子：
6.8
作者：
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通讯作者：
Sham, Pak Chung
影响因子：
11
作者：
Datta, S. R.;McQuillin, A.;Gurling, H. M. D.
通讯作者：
Gurling, H. M. D.
影响因子：
3.3
作者：
Händel, M;Schulz, S;Höllt, V
通讯作者：
Höllt, V
DOI：
10.1093/database/bap022
发表时间：
2009
期刊：
Database : the journal of biological databases and curation
影响因子：
--
作者：
Arnaiz O;Malinowska A;Klotz C;Sperling L;Dadlez M;Koll F;Cohen J
通讯作者：
Cohen J