TY - JOUR
T1 - Loss of Cldn5 -and increase in Irf7-in the hippocampus and cerebral cortex of diabetic mice at the early symptomatic stage
AU - Carús-Cadavieco, Marta
AU - González de la Fuente, Sandra
AU - Berenguer López, Inés
AU - Serrano-Lope, Miguel A.
AU - Aguado, Begoña
AU - Guix, Francesc
AU - Palomer, Ernest
AU - Dotti, Carlos G.
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/8/15
Y1 - 2024/8/15
N2 - 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-3 alpha), period circadian clock 2 (Per2), xanthine dehydrogenase (Xdh), and Transforming growth factor beta-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 I kappa B alpha, implying the involvement of NF-kappa B 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-kappa B pathways underlie cognitive impairment in individuals with long-standing T2DM
AB - 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-3 alpha), period circadian clock 2 (Per2), xanthine dehydrogenase (Xdh), and Transforming growth factor beta-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 I kappa B alpha, implying the involvement of NF-kappa B 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-kappa B pathways underlie cognitive impairment in individuals with long-standing T2DM
KW - Cognitive performance
UR - http://www.scopus.com/inward/record.url?scp=85201405666&partnerID=8YFLogxK
U2 - 10.1038/s41387-024-00325-y
DO - 10.1038/s41387-024-00325-y
M3 - Article
C2 - 39147772
AN - SCOPUS:85201405666
SN - 2044-4052
VL - 14
JO - Nutrition and Diabetes
JF - Nutrition and Diabetes
IS - 1
M1 - 64
ER -