Transcriptomic analysis reveals potential targets associated with hippocampus vulnerability in spatial cognitive dysfunction of type 2 diabetes mellitus rats

IF 2.9 3区医学 Q2 NEUROSCIENCES

Neuroscience Pub Date : 2025-05-25 DOI:10.1016/j.neuroscience.2025.05.036

Ying Zhang , Dongmei Su , Yuru Liu , Bin He , Huiping Wang , Cuige Shi , Yishu Yang

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引用次数: 0

Abstract

Background

Cognitive dysfunction is one of the major complications of T2DM. However, the precise molecular mechanism underlying this relationship remains unclear. Present study aimed to identify potential predictors of cognitive dysfunction associated with T2DM specifically within the hippocampus.

Methods

T2DM was induced by a high-fat diet combined with streptozotocin injections. Morris water maze was employed to assess spatial cognitive ability. HE staining was used to evaluate neurons injury in hippocampus. Transcriptome sequencing was conducted on the hippocampus to identify potential genes. The results obtained from sequencing analysis were validated using qRT-PCR. GO and KEGG analyses were performed to investigate the functions of differentially expressed genes (DEGs) and their associated biological pathways.

Results

Compared with CON rats, the spatial cognitive ability decreased in T2DM rats. Hippocampus neurons reduced in CA1 area of T2DM rats. In total, 123 DEGs were identified by transcriptome sequencing, including 25 upregulated genes and 98 downregulated genes. The qRT-PCR results verified the RNA-seq. KEGG pathway analysis showed the major enriched pathways were TNF signaling pathway, arachidonic acid metabolism, AGE-RAGE signaling pathway in diabetic complications, and cellular senescence. GO analysis showed that DEGs involved in biological process were mainly related to vasculogenesis, response to hypoxia, regulation of cell proliferation and aging.

Conclusions

Our transcriptomic analysis reveals the “cellular senescence” signaling pathway may be implicated in T2DM-induced spatial cognitive dysfunction and Tgfbr2 may be the important DEG involved in this pathway, which will be the primary focus of our future research endeavors.

查看原文本刊更多论文

转录组学分析揭示了与2型糖尿病大鼠空间认知功能障碍海马易感性相关的潜在靶点。

背景：认知功能障碍是T2DM的主要并发症之一。然而，这种关系背后的精确分子机制尚不清楚。本研究旨在明确海马区与T2DM相关的认知功能障碍的潜在预测因素。方法：采用高脂饮食联合注射链脲佐菌素诱导T2DM。Morris水迷宫测试空间认知能力。HE染色观察海马神经元损伤情况。对海马进行转录组测序以鉴定潜在基因。测序分析结果采用qRT-PCR进行验证。采用GO和KEGG分析来研究差异表达基因（DEGs）的功能及其相关的生物学途径。结果：与对照组相比，T2DM大鼠空间认知能力下降。T2DM大鼠海马CA1区神经元减少。通过转录组测序共鉴定出123个基因，包括25个上调基因和98个下调基因。qRT-PCR结果验证了RNA-seq。KEGG通路分析显示，主要富集通路为TNF信号通路、花生四烯酸代谢通路、糖尿病并发症中的AGE-RAGE信号通路和细胞衰老。氧化石墨烯分析显示，参与生物过程的DEGs主要与血管生成、缺氧反应、细胞增殖调控和衰老有关。结论：我们的转录组学分析表明，“细胞衰老”信号通路可能与t2dm诱导的空间认知功能障碍有关，Tgfbr2可能是该通路中重要的DEG，这将是我们未来研究的重点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neuroscience 医学-神经科学

CiteScore

6.20

自引率

0.00%

发文量

394

审稿时长

52 days

期刊介绍： Neuroscience publishes papers describing the results of original research on any aspect of the scientific study of the nervous system. Any paper, however short, will be considered for publication provided that it reports significant, new and carefully confirmed findings with full experimental details.