Prodromic Inflammatory-Oxidative Stress in Peritoneal Leukocytes of Triple-Transgenic Mice for Alzheimer's Disease
Ceprián, Noemí (Universidad Complutense de Madrid. Departamento de Genética, Fisiología y Microbiología)
Martínez de Toda, Irene (Universidad Complutense de Madrid. Departamento de Genética, Fisiología y Microbiología)
Maté, Ianire (Universidad del País Vasco. Departamento de Inmunología, Microbiología y Parasitología)
Garrido, Antonio (Universidad Europea de Madrid. Departamento de Biociencias (Madrid))
Gimenez-Llort, Lydia (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal)
De la Fuente, Mónica (Universidad Complutense de Madrid. Departamento de Genética, Fisiología y Microbiología)

Data:	2024
Resum:	Inflammatory-oxidative stress is known to be pivotal in the pathobiology of Alzheimer's disease (AD), but the involvement of this stress at the peripheral level in the disease's onset has been scarcely studied. This study investigated the pro-inflammatory profile and oxidative stress parameters in peritoneal leukocytes from female triple-transgenic mice for AD (3xTgAD) and non-transgenic mice (NTg). Peritoneal leukocytes were obtained at 2, 4, 6, 12, and 15 months of age. The concentrations of TNFα, INFγ, IL-1β, IL-2, IL-6, IL-17, and IL-10 released in cultures without stimuli and mitogen concanavalin A and lipopolysaccharide presence were measured. The concentrations of reduced glutathione (GSH), oxidized glutathione (GSSG), lipid peroxidation, and Hsp70 were also analyzed in the peritoneal cells. Our results showed that although there was a lower release of pro-inflammatory cytokines by 3xTgAD mice, this response was uncontrolled and overstimulated, especially at a prodromal stage at 2 months of age. In addition, there were lower concentrations of GSH in leukocytes from 3xTgAD and higher amounts of lipid peroxides at 2 and 4 months, as well as, at 6 months, a lower concentration of Hsp70. In conclusion, 3xTgAD mice show a worse pro-inflammatory response and higher oxidative stress than NTg mice during the prodromal stages, potentially supporting the idea that Alzheimer's disease could be a consequence of peripheral alteration in the leukocyte inflammation-oxidation state.
Ajuts:	Ministerio de Ciencia e Innovación BFU2011-30336 Ministerio de Economía y Competitividad PI15/01787
Nota:	Altres ajuts: The research group UCM (910379 ENEROINN)
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Cytokines ; Inflammation ; Longevity ; Oxidative damage ; Triple-transgenic mice for Alzheimer's disease (3xTgAD)
Publicat a:	International journal of molecular sciences, Vol. 25, Num. 13 (June 2024) , ISSN 1422-0067

DOI: 10.3390/ijms25136976
PMID: 39000092

22 p, 4.3 MB

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