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Improvement of cognitive function in wild-type and Alzheimer's disease mouse models by the immunomodulatory properties of menthol inhalation or by depletion of T regulatory cells

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dc.contributor.authorCasares, Noelia
dc.contributor.authorAlfaro Larraya, María
dc.contributor.authorCuadrado-Tejedor, Mar
dc.contributor.authorLasarte-Cía, Aritz
dc.contributor.authorNavarro Negredo, Flor
dc.contributor.authorVivas, Isabel
dc.contributor.authorEspelosín, María
dc.contributor.authorCartas Cejudo, Paz
dc.contributor.authorFernández Irigoyen, Joaquín
dc.contributor.authorSantamaría Martínez, Enrique
dc.contributor.authorGarcía-Osta, Ana
dc.contributor.authorLasarte, Juan José
dc.contributor.departmentCiencias de la Saludes_ES
dc.contributor.departmentOsasun Zientziakeu
dc.date.accessioned2023-10-30T16:35:56Z
dc.date.available2023-10-30T16:35:56Z
dc.date.issued2023
dc.date.updated2023-10-30T15:51:34Z
dc.description.abstractA complex network of interactions exists between the olfactory, immune and central nervous systems. In this work we intend to investigate this connection through the use of an immunostimulatory odorant like menthol, analyzing its impact on the immune system and the cognitive capacity in healthy and Alzheimer’s Disease Mouse Models. We first found that repeated short exposures to menthol odor enhanced the immune response against ovalbumin immunization. Menthol inhalation also improved the cognitive capacity of immunocompetent mice but not in immunodeficient NSG mice, which exhibited very poor fear-conditioning. This improvement was associated with a downregulation of IL-1β and IL-6 mRNA in the brain´s prefrontal cortex, and it was impaired by anosmia induction with methimazole. Exposure to menthol for 6 months (1 week per month) prevented the cognitive impairment observed in the APP/PS1 mouse model of Alzheimer. Besides, this improvement was also observed by the depletion or inhibition of T regulatory cells. Treg depletion also improved the cognitive capacity of the APPNL-G-F/NL-G-F Alzheimer´s mouse model. In all cases, the improvement in learning capacity was associated with a downregulation of IL-1β mRNA. Blockade of the IL-1 receptor with anakinra resulted in a significant increase in cognitive capacity in healthy mice as well as in the APP/PS1 model of Alzheimer´s disease. These data suggest an association between the immunomodulatory capacity of smells and their impact on the cognitive functions of the animals, highlighting the potential of odors and immune modulators as therapeutic agents for CNS-related diseases.en
dc.description.sponsorshipThis work was supported by a grant from the Ministry of Science and Innovation (PID2021-128283OA-I00 financed by MCIN/ AEI /10.13039/501100011033 and by FEDER A way of making Europe and PID2019-104921RB-I00), Department of Economic and Business Development from the Government of Navarra (INNOLFACT project; Ref. 0011-1411-2020-000028) and Explora grant from Ministry of Economy and Competitiveness, (SAF2013-50067-EXP to JL).en
dc.format.mimetypeapplication/pdfen
dc.identifier.citationCasares, N., Alfaro, M., Cuadrado-Tejedor, M., Lasarte-Cia, A., Navarro, F., Vivas, I., Espelosin, M., Cartas-Cejudo, P., Fernández-Irigoyen, J., Santamaría, E., García-Osta, A., & Lasarte, J. J. (2023). Improvement of cognitive function in wild-type and Alzheimer´s disease mouse models by the immunomodulatory properties of menthol inhalation or by depletion of T regulatory cells. Frontiers in Immunology, 14, 1130044. https://doi.org/10.3389/fimmu.2023.1130044en
dc.identifier.doi10.3389/fimmu.2023.1130044
dc.identifier.issn1664-3224
dc.identifier.urihttps://academica-e.unavarra.es/handle/2454/46687
dc.language.isoengen
dc.publisherFrontiers Mediaen
dc.relation.ispartofFrontiers in Immunology 2023, 14:1130044en
dc.relation.projectIDinfo:eu-repo/grantAgreement/AEI//PID2021-128283OA-I00en
dc.relation.projectIDinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-104921RB-I00/ES/en
dc.relation.projectIDinfo:eu-repo/grantAgreement/MINECO//SAF2013-50067-EXP/ES/en
dc.relation.projectIDinfo:eu-repo/grantAgreement/Gobierno de Navarra//0011-1411-2020-000028en
dc.relation.publisherversionhttps://doi.org/10.3389/fimmu.2023.1130044
dc.rightsEspelosin, Cartas-Cejudo, Fernádez-Irigoyen, Santamaría, García -Osta and Lasarte. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).en
dc.rights.accessRightsAcceso abierto / Sarbide irekiaes
dc.rights.accessRightsinfo:eu-repo/semantics/openAccessen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectAlzheimer´s diseaseen
dc.subjectCentral nervous systemen
dc.subjectCognitive capacityen
dc.subjectImmunomodulationen
dc.subjectMentholen
dc.subjectMethimazoleen
dc.subjectOlfactory systemen
dc.subjectTreg cellsen
dc.titleImprovement of cognitive function in wild-type and Alzheimer's disease mouse models by the immunomodulatory properties of menthol inhalation or by depletion of T regulatory cellsen
dc.typeArtículo / Artikuluaes
dc.typeinfo:eu-repo/semantics/articleen
dc.type.versionVersión publicada / Argitaratu den bertsioaes
dc.type.versioninfo:eu-repo/semantics/publishedVersionen
dspace.entity.typePublication
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relation.isAuthorOfPublicationda1d0e22-8279-4c6c-a7c5-cef564dc9542
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relation.isAuthorOfPublication.latestForDiscovery4c3c1bb9-1830-498e-91dc-a7cab5e41d49

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