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慢性锂治疗对海马祖细胞的影响:转录组分析与系统药理学

The effect of chronic lithium treatment on hippocampal progenitor cells: Transcriptomic analysis and systems pharmacology.

作者信息

Jahandideh Mina, Ebrahimi Erfan, Farzaei Mohammad Hosein, Barzegari Ebrahim

机构信息

Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran.

出版信息

Brain Behav. 2023 Oct;13(10):e3215. doi: 10.1002/brb3.3215. Epub 2023 Aug 8.

DOI:10.1002/brb3.3215
PMID:37553827
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10570482/
Abstract

OBJECTIVE

To identify the genomics underpinning the increased volume of the hippocampus after long-term administration of lithium (Li) in bipolar disorder patients, hypothesizing the possible contribution of cell growth and differentiation pathways to this complication.

METHODS

RNA-seq profiles of four samples of hippocampal progenitor cells chronically treated with a high dose of Li and three samples chronically treated with the therapeutic dose were retrieved from NCBI-GEO. The raw data underwent filtration, quality control, expression fold change, adjusted significance, functional enrichment, and pharmacogenomic analyses.

RESULTS

CCND1, LOXL2, and PRNP were identified as the genes involved in the drug response and the chronic effects of Li in the hippocampal cells. GSK-3β was also a hub in the pharmacogenomic network of Li. In addition, ZMPSTE24 and DHX35 were identified as the important genes in lithium therapy.

CONCLUSIONS

As shown by gene ontology results, these findings conclude that lithium may increase the size of the hippocampus in bipolar patients by stimulating the generation of new neurons and promoting their differentiation into neuroblasts, neurons, or microglia.

摘要

目的

确定双相情感障碍患者长期服用锂盐(Li)后海马体体积增加的基因组学基础,推测细胞生长和分化途径对这一并发症的可能作用。

方法

从NCBI-GEO数据库中检索了四个用高剂量Li长期处理的海马祖细胞样本和三个用治疗剂量长期处理的样本的RNA测序图谱。对原始数据进行过滤、质量控制、表达倍数变化、校正显著性、功能富集和药物基因组学分析。

结果

CCND1、LOXL2和PRNP被确定为参与药物反应以及Li对海马细胞慢性作用的基因。GSK-3β也是Li药物基因组网络中的一个枢纽。此外,ZMPSTE24和DHX35被确定为锂盐治疗中的重要基因。

结论

基因本体结果表明,这些发现得出结论,锂盐可能通过刺激新神经元的产生并促进其分化为神经母细胞、神经元或小胶质细胞,从而增加双相情感障碍患者海马体的大小。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f348/10570482/0a5a3eb7532f/BRB3-13-e3215-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f348/10570482/4751a403d8e2/BRB3-13-e3215-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f348/10570482/96354aff983e/BRB3-13-e3215-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f348/10570482/4590f8d2a2ec/BRB3-13-e3215-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f348/10570482/c47db926179b/BRB3-13-e3215-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f348/10570482/0a5a3eb7532f/BRB3-13-e3215-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f348/10570482/4751a403d8e2/BRB3-13-e3215-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f348/10570482/96354aff983e/BRB3-13-e3215-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f348/10570482/4590f8d2a2ec/BRB3-13-e3215-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f348/10570482/c47db926179b/BRB3-13-e3215-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f348/10570482/0a5a3eb7532f/BRB3-13-e3215-g005.jpg

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GSK3β is a critical, druggable component of the network regulating the active NOTCH1 protein and cell viability in CLL.GSK3β 是调控 CLL 中活跃 NOTCH1 蛋白和细胞活力的网络的关键可药物靶点。
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Lithium modulates multiple tau kinases with distinct effects in cortical and hippocampal neurons according to concentration ranges.锂根据浓度范围调节皮质和海马神经元中具有不同作用的多种 tau 激酶。
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Lithium treatment and human hippocampal neurogenesis.锂治疗与人类海马神经发生。
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