LOSS OF CLDN5 -AND INCREASE IN IRF7- IN THE HIPPOCAMPUS AND CEREBRAL CORTEX OF DIABETIC MICE AT THE EARLY SYMPTOMATIC STAGE.

Carus-Cadavieco, M.; Gonzalez de la Fuente, S.; Berenguer, I.; Serrano-Lope, M. A.; Aguado, B.; Palomer, E.; Guix, F.; Dotti, C. G.

doi:10.1101/2023.11.02.565280

bioRxiv · 10.1101/2023.11.02.565280

LOSS OF CLDN5 -AND INCREASE IN IRF7- IN THE HIPPOCAMPUS AND CEREBRAL CORTEX OF DIABETIC MICE AT THE EARLY SYMPTOMATIC STAGE.

Carus-Cadavieco, M.·Gonzalez de la Fuente, S.·Berenguer, I.·Serrano-Lope, M. A.·Aguado, B.·Palomer, E.·Guix, F.·Dotti, C. G.

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Abstract

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 that may underlie the progression toward a more severe phenotype, for example as when individuals age. Here, we present evidence that adult mice with long-term type 2 diabetes mellitus (T2DM) and minor cognitive deficits display alterations in the expression of 27 genes in the cerebral cortex and 16 genes in the hippocampus compared to non-T2DM mice. Only six of these genes undergo the same type of change both in the cortex and hippocampus: Interferon regulatory factor 7 (Irf7), Hypoxia-inducible factor 3 alpha (Hif-3), period circadian clock 2 (Per2), xanthine dehydrogenase (Xdh), and Transforming growth factor {beta}-stimulated clone 22/TSC22 (Tscd3) are all upregulated, while Claudin-5 (Cldn5) is downregulated. At the protein level, Claudin5 and IRF7 showed equivalente changes: downregulation of CLDN5 and upregulation of IRF7. These results suggest that cognitive deficits linked to chronic T2DM may stem from compromised blood-brain barrier integrity and an abnormal inflammatory response in the early stages of the disease. This underscores the potential for therapeutic interventions targeting CLDN5 and IRF7.

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Carus-Cadavieco, M., Gonzalez de la Fuente, S., Berenguer, I., Serrano-Lope, M. A., Aguado, B., Palomer, E., Guix, F., Dotti, C. G.. 2023-11-04. LOSS OF CLDN5 -AND INCREASE IN IRF7- IN THE HIPPOCAMPUS AND CEREBRAL CORTEX OF DIABETIC MICE AT THE EARLY SYMPTOMATIC STAGE.. https://doi.org/10.1101/2023.11.02.565280

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