Marta Carús-Cadavieco, Sandra González de la Fuente, Inés Berenguer López, Miguel A Serrano-Lope, Begoña Aguado, Francesc Guix, Ernest Palomer, Carlos G Dotti
{"title":"糖尿病小鼠早期症状阶段海马和大脑皮层中 Cldn5 的缺失和 Irf7 的增加。","authors":"Marta Carús-Cadavieco, Sandra González de la Fuente, Inés Berenguer López, Miguel A Serrano-Lope, Begoña Aguado, Francesc Guix, Ernest Palomer, Carlos G Dotti","doi":"10.1038/s41387-024-00325-y","DOIUrl":null,"url":null,"abstract":"<p><p>Analyzing changes in gene expression within specific brain regions of individuals with Type 2 Diabetes (T2DM) who do not exhibit significant cognitive deficits can yield valuable insights into the mechanisms underlying the progression towards a more severe phenotype. In this study, transcriptomic analysis of the cortex and hippocampus of mice with long-term T2DM revealed alterations in the expression of 28 genes in the cerebral cortex and 15 genes in the hippocampus. Among these genes, six displayed consistent changes in both the cortex and hippocampus: Interferon regulatory factor 7 (Irf7), Hypoxia-inducible factor 3 alpha (Hif-3α), period circadian clock 2 (Per2), xanthine dehydrogenase (Xdh), and Transforming growth factor β-stimulated clone 22/TSC22 (Tsc22d3) were upregulated, while Claudin-5 (Cldn5) was downregulated. Confirmation of these changes was achieved through RT-qPCR. At the protein level, CLDN5 and IRF7 exhibited similar alterations, with CLDN5 being downregulated and IRF7 being upregulated. In addition, the hippocampus and cortex of the T2DM mice showed decreased levels of IκBα, implying the involvement of NF-κB pathways as well. Taken together, these results suggest that the weakening of the blood-brain barrier and an abnormal inflammatory response via the Interferon 1 and NF-κB pathways underlie cognitive impairment in individuals with long-standing T2DM.</p>","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":null,"pages":null},"PeriodicalIF":4.6000,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11327336/pdf/","citationCount":"0","resultStr":"{\"title\":\"Loss of Cldn5 -and increase in Irf7-in the hippocampus and cerebral cortex of diabetic mice at the early symptomatic stage.\",\"authors\":\"Marta Carús-Cadavieco, Sandra González de la Fuente, Inés Berenguer López, Miguel A Serrano-Lope, Begoña Aguado, Francesc Guix, Ernest Palomer, Carlos G Dotti\",\"doi\":\"10.1038/s41387-024-00325-y\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Analyzing changes in gene expression within specific brain regions of individuals with Type 2 Diabetes (T2DM) who do not exhibit significant cognitive deficits can yield valuable insights into the mechanisms underlying the progression towards a more severe phenotype. In this study, transcriptomic analysis of the cortex and hippocampus of mice with long-term T2DM revealed alterations in the expression of 28 genes in the cerebral cortex and 15 genes in the hippocampus. Among these genes, six displayed consistent changes in both the cortex and hippocampus: Interferon regulatory factor 7 (Irf7), Hypoxia-inducible factor 3 alpha (Hif-3α), period circadian clock 2 (Per2), xanthine dehydrogenase (Xdh), and Transforming growth factor β-stimulated clone 22/TSC22 (Tsc22d3) were upregulated, while Claudin-5 (Cldn5) was downregulated. Confirmation of these changes was achieved through RT-qPCR. At the protein level, CLDN5 and IRF7 exhibited similar alterations, with CLDN5 being downregulated and IRF7 being upregulated. In addition, the hippocampus and cortex of the T2DM mice showed decreased levels of IκBα, implying the involvement of NF-κB pathways as well. 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Loss of Cldn5 -and increase in Irf7-in the hippocampus and cerebral cortex of diabetic mice at the early symptomatic stage.
Analyzing changes in gene expression within specific brain regions of individuals with Type 2 Diabetes (T2DM) who do not exhibit significant cognitive deficits can yield valuable insights into the mechanisms underlying the progression towards a more severe phenotype. In this study, transcriptomic analysis of the cortex and hippocampus of mice with long-term T2DM revealed alterations in the expression of 28 genes in the cerebral cortex and 15 genes in the hippocampus. Among these genes, six displayed consistent changes in both the cortex and hippocampus: Interferon regulatory factor 7 (Irf7), Hypoxia-inducible factor 3 alpha (Hif-3α), period circadian clock 2 (Per2), xanthine dehydrogenase (Xdh), and Transforming growth factor β-stimulated clone 22/TSC22 (Tsc22d3) were upregulated, while Claudin-5 (Cldn5) was downregulated. Confirmation of these changes was achieved through RT-qPCR. At the protein level, CLDN5 and IRF7 exhibited similar alterations, with CLDN5 being downregulated and IRF7 being upregulated. In addition, the hippocampus and cortex of the T2DM mice showed decreased levels of IκBα, implying the involvement of NF-κB pathways as well. Taken together, these results suggest that the weakening of the blood-brain barrier and an abnormal inflammatory response via the Interferon 1 and NF-κB pathways underlie cognitive impairment in individuals with long-standing T2DM.
期刊介绍:
Nutrition & Diabetes is a peer-reviewed, online, open access journal bringing to the fore outstanding research in the areas of nutrition and chronic disease, including diabetes, from the molecular to the population level.