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成年雄性尼罗罗非鱼血清素神经元中阻遏元件1沉默转录因子（REST）的表达

Expression of Repressor Element 1 Silencing Transcription Factor (REST) in Serotonin Neurons in the Adult Male Nile Tilapia ().

作者信息

Soga Tomoko, Nakajima Shingo, Parhar Ishwar S

机构信息

Brain Research Institute Monash Sunway (BRIMS), Jeffery Cheah School of Medicine and Health Sciences, Monash University Malaysia, Selangor, Malaysia.

出版信息

Front Neuroanat. 2021 Mar 11;14:599540. doi: 10.3389/fnana.2020.599540. eCollection 2020.

DOI:10.3389/fnana.2020.599540
PMID:33776659
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7990894/
Abstract

Repressor element-1 silencing transcription factor (REST) is highly expressed in the dorsal raphe where serotonin (5-hydroxytryptamine, 5-HT) neurons are located. REST works as a transcription factor for the 5-HT receptor and tryptophan hydroxylase two-gene expression. We hypothesized that REST is co-expressed in 5-HT neurons, which, if demonstrated, would be useful to understand the mechanism of 5-HT dysfunction-related disorders such as negative emotions and depression. Therefore, the present study was designed to examine the expression of the gene in the brain (forebrain, midbrain, and hindbrain) of adult male Nile tilapia () using rt-PCR. Besides, using immunocytochemistry, co-localization of the gene was examined in 5-HT neurons and with neuronal-/glial-cell markers. We found a high expression of the gene in the midbrain region of the dorsal raphe, an area of 5-HT neurons. Double-label immunocytochemistry showed neuron-specific expression of co-localized in 5-HT neurons in the dorsal and ventral parts of the periventricular pretectal nucleus, paraventricular organ, and dorsal and medial raphe nucleus. Since midbrain 5-HT neurons express REST, we speculate that REST may control 5-HT neuronal activity related to negative emotions, including depression.

摘要

抑制元件-1沉默转录因子（REST）在5-羟色胺（5-HT）能神经元所在的中缝背核中高表达。REST作为5-HT受体和色氨酸羟化酶两个基因表达的转录因子。我们推测REST在5-HT能神经元中共同表达，若得到证实，将有助于理解与5-HT功能障碍相关的疾病（如负面情绪和抑郁症）的发病机制。因此，本研究旨在利用逆转录聚合酶链反应（rt-PCR）检测成年雄性尼罗罗非鱼（）大脑（前脑、中脑和后脑）中该基因的表达。此外，采用免疫细胞化学方法，检测该基因在5-HT能神经元中以及与神经元/神经胶质细胞标志物的共定位情况。我们发现在中缝背核的中脑区域（一个5-HT能神经元区域）该基因有高表达。双标免疫细胞化学显示，在室周顶盖前核、室旁器官以及中缝背核背侧和内侧部分的5-HT能神经元中，该基因呈神经元特异性表达且共定位。由于中脑5-HT能神经元表达REST，我们推测REST可能控制与包括抑郁症在内的负面情绪相关的5-HT能神经元活动。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78c6/7990894/bf19773dfe9e/fnana-14-599540-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78c6/7990894/a9147f940e23/fnana-14-599540-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78c6/7990894/d12a594abc61/fnana-14-599540-g0002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78c6/7990894/964b8f5ece8e/fnana-14-599540-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78c6/7990894/bf19773dfe9e/fnana-14-599540-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78c6/7990894/a9147f940e23/fnana-14-599540-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78c6/7990894/d12a594abc61/fnana-14-599540-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78c6/7990894/5ed9eecb5d23/fnana-14-599540-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78c6/7990894/964b8f5ece8e/fnana-14-599540-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78c6/7990894/bf19773dfe9e/fnana-14-599540-g0005.jpg

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本文引用的文献

1
Repressor element 1 silencing transcription factor /neuron-restrictive silencing factor (REST/NRSF) in social stress and depression.抑制元件 1 沉默转录因子/神经元限制沉默因子（REST/NRSF）在社会应激和抑郁中的作用。
Prog Neuropsychopharmacol Biol Psychiatry. 2021 Jan 10;104:110053. doi: 10.1016/j.pnpbp.2020.110053. Epub 2020 Jul 31.
2
Chronic Social Defeat Stress Up-Regulates Spexin in the Brain of Nile Tilapia (Oreochromis niloticus).慢性社会挫败应激会在上尼罗尖吻鲈（Oreochromis niloticus）的脑中上调 Spexin 的表达。
Sci Rep. 2020 May 6;10(1):7666. doi: 10.1038/s41598-020-64639-4.
3
The transcription factor REST up-regulates tyrosine hydroxylase and antiapoptotic genes and protects dopaminergic neurons against manganese toxicity.
转录因子 REST 上调酪氨酸羟化酶和抗凋亡基因，保护多巴胺能神经元免受锰毒性的侵害。
J Biol Chem. 2020 Mar 6;295(10):3040-3054. doi: 10.1074/jbc.RA119.011446. Epub 2020 Jan 30.
4
The Role of Glutamatergic and Dopaminergic Neurons in the Periaqueductal Gray/Dorsal Raphe: Separating Analgesia and Anxiety.谷氨酸能和多巴胺能神经元在中脑导水管周围灰质/中缝背核中的作用：分离镇痛和焦虑。
eNeuro. 2019 Feb 19;6(1). doi: 10.1523/ENEURO.0018-18.2019. eCollection 2019 Jan-Feb.
5
REST and Neural Gene Network Dysregulation in iPSC Models of Alzheimer's Disease.阿尔茨海默病 iPSC 模型中的 REST 和神经基因网络失调。
Cell Rep. 2019 Jan 29;26(5):1112-1127.e9. doi: 10.1016/j.celrep.2019.01.023.
6
Social Defeat Stress Decreases mRNA for Monoamine Oxidase A and Increases 5-HT Turnover in the Brain of Male Nile Tilapia ().社会挫败应激降低雄性尼罗罗非鱼大脑中单胺氧化酶A的mRNA水平并增加5-羟色胺的周转率。
Front Pharmacol. 2019 Jan 9;9:1549. doi: 10.3389/fphar.2018.01549. eCollection 2018.
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Loss of nuclear REST/NRSF in aged-dopaminergic neurons in Parkinson's disease patients.帕金森病患者中衰老多巴胺能神经元的核 REST/NRSF 丢失。
Neurosci Lett. 2019 Apr 23;699:59-63. doi: 10.1016/j.neulet.2019.01.042. Epub 2019 Jan 23.
8
Expression of RING Finger Protein 38 in Serotonergic Neurons in the Brain of Nile Tilapia, .尼罗罗非鱼脑中血清素能神经元中环状指蛋白38的表达
Front Neuroanat. 2018 Dec 6;12:109. doi: 10.3389/fnana.2018.00109. eCollection 2018.
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Sertraline, chlorprothixene, and chlorpromazine characteristically interact with the REST-binding site of the corepressor mSin3, showing medulloblastoma cell growth inhibitory activities.舍曲林、氯普噻吨和氯丙嗪的特征在于与核心抑制物 mSin3 的 REST 结合位点相互作用，表现出神经母细胞瘤细胞生长抑制活性。
Sci Rep. 2018 Sep 13;8(1):13763. doi: 10.1038/s41598-018-31852-1.
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REST, a master transcriptional regulator in neurodegenerative disease.REST，神经退行性疾病中的主要转录调控因子。
Curr Opin Neurobiol. 2018 Feb;48:193-200. doi: 10.1016/j.conb.2017.12.008. Epub 2018 Jan 30.