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Article

Effects of Low-Intensity Pulsed Ultrasound-Induced Blood–Brain Barrier Opening in P301S Mice Modeling Alzheimer’s Disease Tauopathies

by
Amandine Géraudie
1,*,†,
Maximilien Riche
1,2,3,4,†,
Thaïs Lestra
1,
Alexandre Trotier
1,
Léo Dupuis
1,5,6,
Bertrand Mathon
1,2,3,4,
Alexandre Carpentier
2,3,4 and
Benoît Delatour
1
1
Paris Brain Institute, ICM, Inserm U1127, CNRS UMR 7225, Sorbonne University, 75013 Paris, France
2
Department of Neurosurgery, Sorbonne University, APHP, La Pitié-Salpêtrière Hospital, 75013 Paris, France
3
Faculty of Medicine, Sorbonne University, GRC 23, Brain Machine Interface, APHP, La Pitié-Salpêtrière Hospital, 75013 Paris, France
4
Advanced Surgical Research Technology Lab, Sorbonne University, 75013 Paris, France
5
Laboratoire Des Maladies Neurodégénératives, Université Paris-Saclay, CEA, CNRS, 18 Route du Panorama, 92265 Fontenay-Aux-Roses, France
6
Commissariat à l’Energie Atomique et aux Énergies Alternatives (CEA), Direction de la Recherche Fondamentale (DRF), Institut François Jacob, MIRCen, 18 Route du Panorama, 92265 Fontenay-aux-Roses, France
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Int. J. Mol. Sci. 2023, 24(15), 12411; https://doi.org/10.3390/ijms241512411
Submission received: 29 June 2023 / Revised: 24 July 2023 / Accepted: 28 July 2023 / Published: 3 August 2023
(This article belongs to the Special Issue Transgenic Mice in Human Diseases: Insights from Molecular Research 4.0)
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Abstract

Alzheimer’s disease (AD) is the leading cause of dementia. No treatments have led to clinically meaningful impacts. A major obstacle for peripherally administered therapeutics targeting the central nervous system is related to the blood–brain barrier (BBB). Ultrasounds associated with microbubbles have been shown to transiently and safely open the BBB. In AD mouse models, the sole BBB opening with no adjunct drugs may be sufficient to reduce lesions and mitigate cognitive decline. However, these therapeutic effects are for now mainly assessed in preclinical mouse models of amyloidosis and remain less documented in tau lesions. The aim of the present study was therefore to evaluate the effects of repeated BBB opening using low-intensity pulsed ultrasounds (LIPU) in tau transgenic P301S mice with two main readouts: tau-positive lesions and microglial cells. Our results show that LIPU-induced BBB opening does not decrease tau pathology and may even potentiate the accumulation of pathological tau in selected brain regions. In addition, LIPU-BBB opening in P301S mice strongly reduced microglia densities in brain parenchyma, suggesting an anti-inflammatory action. These results provide a baseline for future studies using LIPU-BBB opening, such as adjunct drug therapies, in animal models and in AD patients.
Keywords: Alzheimer’s disease; tauopathies; BBB opening; low-intensity pulsed ultrasounds Alzheimer’s disease; tauopathies; BBB opening; low-intensity pulsed ultrasounds

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MDPI and ACS Style

Géraudie, A.; Riche, M.; Lestra, T.; Trotier, A.; Dupuis, L.; Mathon, B.; Carpentier, A.; Delatour, B. Effects of Low-Intensity Pulsed Ultrasound-Induced Blood–Brain Barrier Opening in P301S Mice Modeling Alzheimer’s Disease Tauopathies. Int. J. Mol. Sci. 2023, 24, 12411. https://doi.org/10.3390/ijms241512411

AMA Style

Géraudie A, Riche M, Lestra T, Trotier A, Dupuis L, Mathon B, Carpentier A, Delatour B. Effects of Low-Intensity Pulsed Ultrasound-Induced Blood–Brain Barrier Opening in P301S Mice Modeling Alzheimer’s Disease Tauopathies. International Journal of Molecular Sciences. 2023; 24(15):12411. https://doi.org/10.3390/ijms241512411

Chicago/Turabian Style

Géraudie, Amandine, Maximilien Riche, Thaïs Lestra, Alexandre Trotier, Léo Dupuis, Bertrand Mathon, Alexandre Carpentier, and Benoît Delatour. 2023. "Effects of Low-Intensity Pulsed Ultrasound-Induced Blood–Brain Barrier Opening in P301S Mice Modeling Alzheimer’s Disease Tauopathies" International Journal of Molecular Sciences 24, no. 15: 12411. https://doi.org/10.3390/ijms241512411

APA Style

Géraudie, A., Riche, M., Lestra, T., Trotier, A., Dupuis, L., Mathon, B., Carpentier, A., & Delatour, B. (2023). Effects of Low-Intensity Pulsed Ultrasound-Induced Blood–Brain Barrier Opening in P301S Mice Modeling Alzheimer’s Disease Tauopathies. International Journal of Molecular Sciences, 24(15), 12411. https://doi.org/10.3390/ijms241512411

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