ESTIMULACION DEL SISTEMA NERVIOSO CENTRAL A TRAVES DEL SISTEMA OLFATIVO, COMO METODO DE POTENCIACION DE LA RESPUESTA INMUNE ANTITUMORAL Y ANTIVIRAL
SAF2013-50067-EXP
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Nombre agencia financiadora Ministerio de Economía y Competitividad
Acrónimo agencia financiadora MINECO
Programa Programa Estatal de Fomento de la Investigación Científica y Técnica de Excelencia
Subprograma Subprograma Estatal de Generación del Conocimiento
Convocatoria Proyectos «Explora Ciencia» y «Explora Tecnología»
Año convocatoria 2013
Unidad de gestión Dirección General de Investigación Científica y Técnica
Centro beneficiario FUNDACIÓN PARA LA INVESTIGACIÓN MÉDICA APLICADA (FIMA)
Centro realización CENTRO DE INVESTIGACIÓN MÉDICA APLICADA
Identificador persistente http://dx.doi.org/10.13039/501100003329
Publicaciones
Resultados totales (Incluyendo duplicados): 1
Encontrada(s) 1 página(s)
Encontrada(s) 1 página(s)
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
Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
- Casares, Noelia
- Alfaro Larraya, María
- Cuadrado-Tejedor, Mar
- Lasarte-Cía, Aritz
- Navarro Negredo, Flor
- Vivas, Isabel
- Espelosín, María
- Cartas Cejudo, Paz
- Fernández Irigoyen, Joaquín
- Santamaría Martínez, Enrique
- García-Osta, Ana
- Lasarte, Juan José
A 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., This 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).