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Volume 25
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Article

Early Increase in Blood–Brain Barrier Permeability in a Murine Model Exposed to Fifteen Days of Intermittent Hypoxia

by
Frederic Roche
1,2,*,
Anne Briançon-Marjollet
2,
Maurice Dematteis
2,
Marie Baldazza
2,
Brigitte Gonthier
2,
Frederique Bertholon
3,
Nathalie Perek
1 and
Jean-Louis Pépin
2
1
INSERM, SAINBIOSE U1059, Université Jean Monnet Saint-Étienne, Mines Saint Etienne, F-42023 Saint-Étienne, France
2
INSERM U1300, HP2 Laboratory, Université Grenoble Alpes, F-38042 Grenoble, France
3
Centre de Ressources Biologiques, CHU de Saint Etienne, F-42055 Saint-Étienne, France
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2024, 25(5), 3065; https://doi.org/10.3390/ijms25053065
Submission received: 15 December 2023 / Revised: 8 February 2024 / Accepted: 28 February 2024 / Published: 6 March 2024
(This article belongs to the Collection Feature Papers in Molecular Pathology, Diagnostics, and Therapeutics)
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Abstract

Obstructive sleep apnea (OSA) is characterized by intermittent repeated episodes of hypoxia–reoxygenation. OSA is associated with cerebrovascular consequences. An enhanced blood–brain barrier (BBB) permeability has been proposed as a marker of those disorders. We studied in mice the effects of 1 day and 15 days intermittent hypoxia (IH) exposure on BBB function. We focused on the dorsal part of the hippocampus and attempted to identify the molecular mechanisms by combining in vivo BBB permeability (Evans blue tests) and mRNA expression of several junction proteins (zona occludens (ZO-1,2,3), VE-cadherin, claudins (1,5,12), cingulin) and of aquaporins (1,4,9) on hippocampal brain tissues. After 15 days of IH exposure we observed an increase in BBB permeability, associated with increased mRNA expressions of claudins 1 and 12, aquaporins 1 and 9. IH seemed to increase early for claudin-1 mRNA expression as it doubled with 1 day of exposure and returned near to its base level after 15 days. Claudin-1 overexpression may represent an immediate response to IH exposure. Then, after 15 days of exposure, an increase in functional BBB permeability was associated with enhanced expression of aquaporin. These BBB alterations are possibly associated with a vasogenic oedema that may affect brain functions and accelerate neurodegenerative processes.
Keywords: blood–brain barrier; tight junction; aquaporins; intermittent hypoxia; mice model blood–brain barrier; tight junction; aquaporins; intermittent hypoxia; mice model

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MDPI and ACS Style

Roche, F.; Briançon-Marjollet, A.; Dematteis, M.; Baldazza, M.; Gonthier, B.; Bertholon, F.; Perek, N.; Pépin, J.-L. Early Increase in Blood–Brain Barrier Permeability in a Murine Model Exposed to Fifteen Days of Intermittent Hypoxia. Int. J. Mol. Sci. 2024, 25, 3065. https://doi.org/10.3390/ijms25053065

AMA Style

Roche F, Briançon-Marjollet A, Dematteis M, Baldazza M, Gonthier B, Bertholon F, Perek N, Pépin J-L. Early Increase in Blood–Brain Barrier Permeability in a Murine Model Exposed to Fifteen Days of Intermittent Hypoxia. International Journal of Molecular Sciences. 2024; 25(5):3065. https://doi.org/10.3390/ijms25053065

Chicago/Turabian Style

Roche, Frederic, Anne Briançon-Marjollet, Maurice Dematteis, Marie Baldazza, Brigitte Gonthier, Frederique Bertholon, Nathalie Perek, and Jean-Louis Pépin. 2024. "Early Increase in Blood–Brain Barrier Permeability in a Murine Model Exposed to Fifteen Days of Intermittent Hypoxia" International Journal of Molecular Sciences 25, no. 5: 3065. https://doi.org/10.3390/ijms25053065

APA Style

Roche, F., Briançon-Marjollet, A., Dematteis, M., Baldazza, M., Gonthier, B., Bertholon, F., Perek, N., & Pépin, J.-L. (2024). Early Increase in Blood–Brain Barrier Permeability in a Murine Model Exposed to Fifteen Days of Intermittent Hypoxia. International Journal of Molecular Sciences, 25(5), 3065. https://doi.org/10.3390/ijms25053065

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