In silico identification of the potential molecular mechanisms involved in protective effects of prolactin on motor and memory deficits induced by 1,2-Diacetylbenzene in young and old rats

被引:14
作者
Nguyen, Hai Duc [1 ,2 ]
Jo, Won Hee [1 ,2 ]
Hoang, Ngoc Hong Minh [1 ,2 ]
Kim, Min-Sun [1 ,2 ]
机构
[1] Sunchon Natl Univ, Coll Pharm, Dept Pharm, Sunchon 57922, South Korea
[2] Sunchon Natl Univ, Res Inst Life & Pharmaceut Sci, Sunchon 57922, South Korea
基金
新加坡国家研究基金会;
关键词
Prolactin; Motor and memory deficits; 2-Diacetylbenzene; Young and old rats; Molecular mechanisms; PARKINSONS-DISEASE; AGING RATS; XENOBIOTIC METABOLISM; PROTEIN; PITUITARY; BRAIN; EXPRESSION; MUTATIONS; RECEPTORS; SECRETION;
D O I
10.1016/j.neuro.2022.09.002
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
We aimed to identify the molecular mechanisms through which prolactin protects against 1,2-Diacetylbenzene (DAB)-induced memory and motor impairments. The gene expression omnibus database (no. GSE119435), transcriptomic data, GeneMANIA, ToppGeneSuite, Metascape, STRING database, Cytoscape, and Autodock were used as the core tools in in-silico analyses. We observed that prolactin may improve memory and motor deficits caused by DAB via 13 genes (Scn5a, Lmntd1, LOC100360619, Rgs9, Srpk3, Syndig1l, Gpr88, Egr2, Ctxn3, Drd2, Ttr, Gpr6, and Ecel1) in young rats and 9 genes (Scn5a, Chat, RGD1560608, Ucma, Lrrc31, Gpr88, Col1a2, Cnbd1, and Ttr) in old rats. Almost all of these genes were downregulated in both young and old rats given DAB, but they were increased in both young and old rats given prolactin. Co-expression interactions were identified as the most important interactions (83.2 % for young rats and 100 % for old rats). The most important mechanisms associated with prolactin's ability to counteract DAB were identified, including "learning and memory," and "positive regulation of ion transport" in young rats, as well as "acetylcholine related pathways," "inflammatory response pathway," and "neurotransmitter release cycle" in old rats. We also identified several key miRNAs associated with memory and motor deficits, as well as prolactin and DAB exposure (rno-miR-141-3p, rno-miR-200a-3p, rno-miR-124-3p, rno-miR-26, and rno-let-7 families). The most significant transcription factors asso-ciated with differentially expressed gene regulation were Six3, Rxrg, Nkx26, and Tbx20. These findings will contribute to our understanding of the processes through which prolactin's beneficial effects counteract DAB -induced memory and motor deficits.
引用
收藏
页码:45 / 59
页数:15
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