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非病毒色氨酸羟化酶构建体暴露于小鼠脑和 HEK-293 细胞后，5-HT 水平均升高。

Increase of 5-HT levels is induced both in mouse brain and HEK-293 cells following their exposure to a non-viral tryptophan hydroxylase construct.

机构信息

Unidad de Investigación Biomédica en Inmunología e Infectología, Hospital de Infectología, Centro Médico Nacional "La Raza", IMSS, Ciudad de México, México.

Unidad de Investigación Médica en Enfermedades Endócrinas, UMAE, Hospital de Especialidades, Centro Médico Nacional "Siglo XXI", IMSS, Ciudad de México, México.

出版信息

Transl Psychiatry. 2021 Oct 8;11(1):515. doi: 10.1038/s41398-021-01634-x.

DOI:10.1038/s41398-021-01634-x
PMID:34625528
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8501106/
Abstract

Tryptophan hydroxylase type 2 (Tph2) is the rate-limiting enzyme for serotonin (5-HT) biosynthesis in the brain. Dysfunctional Tph2 alters 5-HT biosynthesis, leading to a deficiency of 5-HT, which could have repercussions on human behavior. In the last decade, several studies have associated polymorphisms of the TPH2 gene with suicidal behavior. Additionally, a 5-HT deficiency has been implicated in various psychiatric pathologies, including alcoholism, impulsive behavior, anxiety, and depression. Therefore, the TPH2 gene could be an ideal target for analyzing the effects of a 5-HT deficiency on brain function. The aim of this study was to use the construct pIRES-hrGFP-1a-Tph2-FLAG to treat CD1-male mice and to transfect HEK-293-cells and then to evaluate whether this treatment increases 5-HT production. 5-HT levels were enhanced 48 h post-transfection, in HEK-293 cells. Three days after the ocular administration of pIRES-hrGFP-1a-Tph2-FLAG to mice, putative 5-HT production was significantly higher than in the control in both hypothalamus and amygdala, but not in the brainstem. Further research will be needed on the possible application of this treatment for psychiatric diseases involving a Tph2 dysfunction or serotonin deficiency.

摘要

色氨酸羟化酶 2（Tph2）是大脑中 5-羟色胺（5-HT）生物合成的限速酶。功能失调的 Tph2 改变 5-HT 的生物合成，导致 5-HT 缺乏，这可能对人类行为产生影响。在过去的十年中，多项研究将 TPH2 基因的多态性与自杀行为联系起来。此外，5-HT 缺乏与各种精神病理学有关，包括酗酒、冲动行为、焦虑和抑郁。因此，TPH2 基因可能是分析 5-HT 缺乏对大脑功能影响的理想靶点。本研究的目的是使用构建体 pIRES-hrGFP-1a-Tph2-FLAG 治疗 CD1 雄性小鼠，并转染 HEK-293 细胞，然后评估这种治疗是否能增加 5-HT 的产生。转染后 48 小时，HEK-293 细胞中的 5-HT 水平增强。在向小鼠眼内给药 pIRES-hrGFP-1a-Tph2-FLAG 3 天后，下丘脑和杏仁核中的 5-HT 产生量明显高于对照组，但脑干中则没有。对于涉及 Tph2 功能障碍或 5-HT 缺乏的精神疾病，有必要进一步研究这种治疗的可能应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec9c/8501106/d723a17fa642/41398_2021_1634_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec9c/8501106/5762c4105ef8/41398_2021_1634_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec9c/8501106/9ff6cf8e24fb/41398_2021_1634_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec9c/8501106/ed3fbc01c8aa/41398_2021_1634_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec9c/8501106/d723a17fa642/41398_2021_1634_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec9c/8501106/5762c4105ef8/41398_2021_1634_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec9c/8501106/9ff6cf8e24fb/41398_2021_1634_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec9c/8501106/ed3fbc01c8aa/41398_2021_1634_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec9c/8501106/d723a17fa642/41398_2021_1634_Fig4_HTML.jpg

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Intranasal Administration of a Naked Plasmid Reached Brain Cells and Expressed Green Fluorescent Protein, a Candidate for Future Gene Therapy Studies.鼻腔内给予裸质粒可到达脑细胞并表达绿色荧光蛋白，这是未来基因治疗研究的候选物。
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