Siyuan Zhu, Yidan Pang, Xiangwei Zhang, Chunying Yang, Junjie Gao, Ping Fang, Yaohui Zhang, Yunjin Yao, Fangyu Ju, Fang Ye, Hongyi Zhu, Peng Liao, Lufeng Yao, Lulu Dai, Jun Xu, Bo Wu, Jun Pan, Yijun Wu
{"title":"Alteration of Thyroid Hormones in Mouse Models of Alzheimer's Disease and Aging.","authors":"Siyuan Zhu, Yidan Pang, Xiangwei Zhang, Chunying Yang, Junjie Gao, Ping Fang, Yaohui Zhang, Yunjin Yao, Fangyu Ju, Fang Ye, Hongyi Zhu, Peng Liao, Lufeng Yao, Lulu Dai, Jun Xu, Bo Wu, Jun Pan, Yijun Wu","doi":"10.1159/000536089","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Aging is characterized by the deterioration of a wide range of functions in tissues and organs, and Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognitive impairment. Hypothyroidism occurs when there is insufficient production of thyroid hormones (THs) by the thyroid. The relationship between hypothyroidism and aging as well as AD is controversial at present.</p><p><strong>Methods: </strong>We established an animal model of AD (FAD4T) with mutations in the APP and PSEN1 genes, and we performed a thyroid function test and RNA sequencing (RNA-Seq) of the thyroid from FAD4T and naturally aging mice. We also studied gene perturbation correlation in the FAD4T mouse thyroid, bone marrow, and brain by further single-cell RNA sequencing (scRNA-seq) data of the bone marrow and brain.</p><p><strong>Results: </strong>In this study, we found alterations in THs in both AD and aging mice. RNA-seq data showed significant upregulation of T-cell infiltration- and cell proliferation-related genes in FAD4T mouse thyroid. In addition, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that upregulated genes were enriched in the functional gene modules of activation of immune cells. Downregulated energy metabolism-related genes were prominent in aging thyroids, which reflected the reduction in THs. GSEA showed a similar enrichment tendency in both mouse thyroids, suggesting their analogous inflammation state. In addition, the regulation of leukocyte activation and migration was a common signature between the thyroid, brain, and bone marrow of FAD4T mice.</p><p><strong>Conclusions: </strong>Our findings identified immune cell infiltration of the thyroid as the potential underlying mechanism of the alteration of THs in AD and aging.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"411-422"},"PeriodicalIF":3.2000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neuroendocrinology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1159/000536089","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/16 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0
Abstract
Introduction: Aging is characterized by the deterioration of a wide range of functions in tissues and organs, and Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognitive impairment. Hypothyroidism occurs when there is insufficient production of thyroid hormones (THs) by the thyroid. The relationship between hypothyroidism and aging as well as AD is controversial at present.
Methods: We established an animal model of AD (FAD4T) with mutations in the APP and PSEN1 genes, and we performed a thyroid function test and RNA sequencing (RNA-Seq) of the thyroid from FAD4T and naturally aging mice. We also studied gene perturbation correlation in the FAD4T mouse thyroid, bone marrow, and brain by further single-cell RNA sequencing (scRNA-seq) data of the bone marrow and brain.
Results: In this study, we found alterations in THs in both AD and aging mice. RNA-seq data showed significant upregulation of T-cell infiltration- and cell proliferation-related genes in FAD4T mouse thyroid. In addition, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that upregulated genes were enriched in the functional gene modules of activation of immune cells. Downregulated energy metabolism-related genes were prominent in aging thyroids, which reflected the reduction in THs. GSEA showed a similar enrichment tendency in both mouse thyroids, suggesting their analogous inflammation state. In addition, the regulation of leukocyte activation and migration was a common signature between the thyroid, brain, and bone marrow of FAD4T mice.
Conclusions: Our findings identified immune cell infiltration of the thyroid as the potential underlying mechanism of the alteration of THs in AD and aging.
期刊介绍：
''Neuroendocrinology'' publishes papers reporting original research in basic and clinical neuroendocrinology. The journal explores the complex interactions between neuronal networks and endocrine glands (in some instances also immunecells) in both central and peripheral nervous systems. Original contributions cover all aspects of the field, from molecular and cellular neuroendocrinology, physiology, pharmacology, and the neuroanatomy of neuroendocrine systems to neuroendocrine correlates of behaviour, clinical neuroendocrinology and neuroendocrine cancers. Readers also benefit from reviews by noted experts, which highlight especially active areas of current research, and special focus editions of topical interest.
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