c80027e209d2e568eb6ecb2a48f6b234 pmc_11241217.pdf 85a23e13cf64b3be0fb599b2d395a48048b8ccd6 pmc_11241217.pdf b319d00f643d54985ad892ece182fd59caa823336102225410b48f291948393c pmc_11241217.pdf Title: Prodromic Inflammatory–Oxidative Stress in Peritoneal Leukocytes of Triple-Transgenic Mice for Alzheimer’s Disease Subject: 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 TNF, INF, IL-1, 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. Keywords: cytokines; inflammation; longevity; oxidative damage; triple-transgenic mice for Alzheimer’s disease (3xTgAD) Author: Noemí Ceprián, Irene Martínez de Toda, Ianire Maté, Antonio Garrido, Lydia Gimenez-Llort and Mónica De la Fuente Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Tue Jul 9 11:26:32 2024 CEST ModDate: Tue Jul 9 11:31:44 2024 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 22 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 4555229 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- JYPLJJ+VnURWPalladioL-Bold Type 1 Custom yes yes yes 10 0 QNWFPZ+EURM10 Type 1 Builtin yes yes yes 16 0 QNPXDJ+URWPalladioL-Bold Type 1 Custom yes yes yes 21 0 XCGKQC+URWPalladioL-Roma Type 1 Custom yes yes yes 27 0 OLJBUO+URWPalladioL-Ital Type 1 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JBMOJM+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 356 0 JBMOJN+PalatinoLinotype CID TrueType Identity-H yes yes yes 359 0 JBMOJO+PalatinoLinotype TrueType WinAnsi yes yes no 365 0 JBMOKA+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 368 0 JBMOPA+PalatinoLinotype TrueType MacRoman yes yes no 371 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2025-02-20 02:13:21 CET RepresentationInformation: pmc_11241217.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2025-02-19 04:54:05 CET Size: 4555229 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 813 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Results Destination: section.2 Children: Item: Title: Inflammatory Stress Destination: subsection.2.1 Item: Title: Oxidative Stress Destination: subsection.2.2 Item: Title: Longevity Destination: subsection.2.3 Item: Title: Discussion Destination: section.3 Item: Title: Materials and Methods Destination: section.4 Children: Item: Title: Animals Destination: subsection.4.1 Item: Title: Experimental Design Destination: subsection.4.2 Item: Title: Collection of Peritoneal Leukocytes Destination: subsection.4.3 Item: Title: Cytokine Measurement Destination: subsection.4.4 Item: Title: Oxidative Damage Destination: subsection.4.5 Item: Title: Protein Quantification Destination: subsection.4.6 Item: Title: Statistical Analysis Destination: subsection.4.7 Item: Title: References Destination: appendix.A. Info: Title: Prodromic Inflammatory Oxidative Stress in Peritoneal Leukocytes of Triple-Transgenic Mice for Alzheimer’s Disease Author: Noemí Ceprián, Irene Martínez de Toda, Ianire Maté, Antonio Garrido, Lydia Gimenez-Llort and Mónica De la Fuente Subject: 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 TNF, INF, IL-1, 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. 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