99b75c85972297bac84bebc10d333461 327800.pdf c118ab6cc9cdb58b33643e3d45ffad16e882ee61 327800.pdf 0e7c67b7984fb4763f30ff9fc148e4761a2f990c926fbcc76e8e619da2f0f610 327800.pdf Title: Peripheral Oxidation-Inflammation and Immunosenescence in Triple-Transgenic Mice for Alzheimer’s Disease (3xTg-AD) at Early Neuropathological Stages of Disease and Decrease of Immune Impairment by Voluntary Exercise Subject: Inflammatory-oxidative stress generated by immune cells plays an important role in aging and in age-related neurodegenerative disorders such as Alzheimer’s disease (AD). Triple-transgenic mice for AD (3xTg-AD) are a suitable model for mimicking this disease in an age-dependent manner. We previously showed that peritoneal leukocyte functions and their redox-inflammatory state are altered early in female 3xTg-AD mice, which exhibit premature aging compared to non-transgenic (NTg) animals. However, their characteristics at 9 months of age, when they present an early neuropathological state, and the sex differences are not known. Here, we analyzed several spleen and thymus leukocyte functions (chemotaxis, natural killer activity, and lymphoproliferation in response to mitogens), pro-inflammatory (IL-1B, TNF-alpha) and anti-inflammatory (IL-10) released cytokine concentrations, and redox parameters (glutathione concentrations and glutathione peroxidase, glutathione reductase, and xanthine oxidase activities) in male and female 3xTg-AD mice compared to age-matched controls. We also analyzed the effects of voluntary physical exercise on immune functions. Our results show that 9-month-old male and female 3xTg-AD mice have worse immune functions, redox state, and inflammation than NTg counterparts. Physical exercise improves immune function. Thus, accelerated aging reflected by peripheral immunosenescence and oxidation-inflammation in 3xTg-AD mice precedes hallmark neuropathology, and exercise can slow down AD progression. Keywords: oxidation-inflammation; immunosenescence; triple-transgenic Alzheimerdisease (3xTg-AD) mouse model; early neuropathological state; physical exercise Author: Mónica De la Fuente, Antonio Garrido, Carmen Vida, Rashed Manassra and Lydia Gimenez-Llort Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25; modified using OpenPDF 1.4.2 CreationDate: Sun Mar 22 13:15:42 2026 CET ModDate: Sun Mar 22 13:35:12 2026 CET Custom Metadata: yes Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 26 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 2000358 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- BECYZK+URWPalladioL-Bold Type 1 Custom yes yes yes 137 0 IXPRJC+URWPalladioL-Roma Type 1 Custom yes yes yes 138 0 MGSNFJ+URWPalladioL-Ital Type 1 Custom yes yes yes 139 0 MIKRSI+VnURWPalladioL Type 1 Custom yes yes yes 140 0 CAMXTK+EURM10 Type 1 Builtin yes yes yes 198 0 MJSSOL+CMSY10 Type 1 Builtin yes yes yes 281 0 MPUDFL+PazoMath Type 1 Builtin yes yes yes 307 0 BJGEGA+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 300 0 BJGEEO+PalatinoLinotype CID TrueType Identity-H yes yes yes 301 0 BJGEEP+PalatinoLinotype TrueType WinAnsi yes yes no 302 0 BJGFOO+PalatinoLinotype,BoldItalic TrueType WinAnsi yes yes no 303 0 BAHEPE+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 344 0 BAHEPC+PalatinoLinotype TrueType WinAnsi yes yes no 345 0 BAHEPE+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 352 0 BAHEPC+PalatinoLinotype TrueType WinAnsi yes yes no 353 0 BAHEPE+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 412 0 BAHEPC+PalatinoLinotype TrueType WinAnsi yes yes no 413 0 BAHEPE+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 452 0 BAHEPC+PalatinoLinotype TrueType WinAnsi yes yes no 453 0 BAHEPE+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 470 0 BAHEPC+PalatinoLinotype TrueType WinAnsi yes yes no 471 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2026-04-23 04:04:50 CEST RepresentationInformation: 327800.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2026-04-22 09:36:47 CEST Size: 2000358 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 882 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: ViewerPreferences: HideToolbar: false HideMenubar: false HideWindowUI: false FitWindow: true CenterWindow: false DisplayDocTitle: false NonFullScreenPageMode: UseNone Direction: L2R ViewArea: CropBox ViewClip: CropBox PrintArea: CropBox PageClip: CropBox PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Item: Title: Materials and Methods Children: Item: Title: Animals Item: Title: Isolation of Leukocytes from Spleen and Thymus Item: Title: Immune Function Parameters Children: Item: Title: Chemotaxis Capacity Item: Title: Natural Killer (NK) Activity Item: Title: Lymphoproliferation Assay Item: Title: Cytokine Concentration Measurements Item: Title: Redox Parameters Children: Item: Title: Reduced Glutathione (GSH) Concentrations Item: Title: Glutathione Peroxidase (GPx) Activity Item: Title: Glutathione Reductase (GR) Activity Item: Title: Xanthine Oxidase Activity Item: Title: Protein Quantification Item: Title: Statistical Analyses Item: Title: Results Children: Item: Title: Sex Differences Item: Title: Effect of Regular Voluntary Exercise Item: Title: Discussion Item: Title: Conclusions Item: Title: References Info: Title: Peripheral Oxidation-Inflammation and Immunosenescence in Triple-Transgenic Mice for Alzheimer’s Disease (3xTg-AD) at Early Neuropathological Stages of Disease and Decrease of Immune Impairment by Voluntary Exercise Author: Mónica De la Fuente, Antonio Garrido, Carmen Vida, Rashed Manassra and Lydia Gimenez-Llort Subject: Inflammatory-oxidative stress generated by immune cells plays an important role in aging and in age-related neurodegenerative disorders such as Alzheimer’s disease (AD). Triple-transgenic mice for AD (3xTg-AD) are a suitable model for mimicking this disease in an age-dependent manner. We previously showed that peritoneal leukocyte functions and their redox-inflammatory state are altered early in female 3xTg-AD mice, which exhibit premature aging compared to non-transgenic (NTg) animals. However, their characteristics at 9 months of age, when they present an early neuropathological state, and the sex differences are not known. Here, we analyzed several spleen and thymus leukocyte functions (chemotaxis, natural killer activity, and lymphoproliferation in response to mitogens), pro-inflammatory (IL-1B, TNF-alpha) and anti-inflammatory (IL-10) released cytokine concentrations, and redox parameters (glutathione concentrations and glutathione peroxidase, glutathione reductase, and xanthine oxidase activities) in male and female 3xTg-AD mice compared to age-matched controls. We also analyzed the effects of voluntary physical exercise on immune functions. Our results show that 9-month-old male and female 3xTg-AD mice have worse immune functions, redox state, and inflammation than NTg counterparts. Physical exercise improves immune function. Thus, accelerated aging reflected by peripheral immunosenescence and oxidation-inflammation in 3xTg-AD mice precedes hallmark neuropathology, and exercise can slow down AD progression. Keywords: oxidation-inflammation; immunosenescence; triple-transgenic Alzheimerdisease (3xTg-AD) mouse model; early neuropathological state; physical exercise Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25; modified using OpenPDF 1.4.2 CreationDate: Sun Mar 22 13:15:42 CET 2026 ModDate: Sun Mar 22 13:35:12 CET 2026 ID: 0x4fb72575fe63e090771aa75cb61ebf47, 0x9ea20b65eb32d2def2b76dae24b9a1cb Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: MPUDFL+PazoMath FontSubset: true FirstChar: 68 LastChar: 68 FontDescriptor: FontName: MPUDFL+PazoMath Flags: Symbolic FontBBox: -40, -283, 878, 946 FontFile: true ToUnicode: true Font: BaseFont: CAMXTK+EURM10 FontSubset: true FirstChar: 12 LastChar: 22 FontDescriptor: FontName: CAMXTK+EURM10 Flags: Symbolic FontBBox: -32, -243, 1060, 720 FontFile: true ToUnicode: true Font: BaseFont: BECYZK+URWPalladioL-Bold FontSubset: true FirstChar: 3 LastChar: 243 FontDescriptor: FontName: BECYZK+URWPalladioL-Bold Flags: Symbolic FontBBox: 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c118ab6cc9cdb58b33643e3d45ffad16e882ee61 Type: SHA-1 Checksum: 0e7c67b7984fb4763f30ff9fc148e4761a2f990c926fbcc76e8e619da2f0f610 Type: SHA-256