1f1d828a99f8528b0b12822e6e059116 pmc_11172848.pdf e9c9d797c23330ef6b283f8ba79229f922dc014a pmc_11172848.pdf ec9dbdcdcef23865e8aec632c073acb751447d1b2110379d799aa3f097923b39 pmc_11172848.pdf Title: Glomerular Hypertrophy and Splenic Red Pulp Degeneration Concurrent with Oxidative Stress in 3xTg-AD Mice Model for Alzheimer’s Disease and Its Exacerbation with Sex and Social Isolation Subject: The continuously expanding field of Alzheimer’s disease (AD) research is now beginning to defocus the brain to take a more systemic approach to the disease, as alterations in the peripheral organs could be related to disease progression. One emerging hypothesis is organ involvement in the process of A clearance. In the present work, we aimed to examine the status and involvement of the kidney as a key organ for waste elimination and the spleen, which is in charge of filtering the blood and producing lymphocytes, and their influence on AD. The results showed morphological and structural changes due to acute amyloidosis in the kidney (glomeruli area) and spleen (red pulp area and red/white pulp ratio) together with reduced antioxidant defense activity (GPx) in 16-month-old male and female 3xTg-AD mice when compared to their age- and sex-matched non-transgenic (NTg) counterparts. All these alterations correlated with the anxious-like behavioral phenotype of this mouse model. In addition, forced isolation, a cause of psychological stress, had a negative effect by intensifying genotype differences and causing differences to appear in NTg animals. This study further supports the relevance of a more integrative view of the complex interplay between systems in aging, especially at advanced stages of Alzheimer’s disease. Keywords: Alzheimer’s disease; peripheric organs; kidney; spleen; amyloidosis; oxidative stress Author: Juan Fraile-Ramos, Josep Reig-Vilallonga and Lydia Giménez-Llort Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Tue Jun 4 10:29:08 2024 CEST ModDate: Tue Jun 4 10:32:13 2024 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 17 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 3296935 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- BTFGED+VnURWPalladioL-Bold Type 1 Custom yes yes yes 10 0 CAMXTK+EURM10 Type 1 Builtin yes yes yes 16 0 RRPWOX+URWPalladioL-Bold Type 1 Custom yes yes yes 21 0 WJMFLO+URWPalladioL-Roma Type 1 Custom yes yes yes 27 0 JCZCAP+URWPalladioL-Ital Type 1 Custom yes yes yes 32 0 YOBNLN+VnURWPalladioL Type 1 Custom yes yes yes 37 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no no no 380 0 JBCRLF+PazoMath Type 1 Builtin yes yes yes 409 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-09-01 08:12:50 CEST RepresentationInformation: pmc_11172848.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2024-07-18 02:30:18 CEST Size: 3296935 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 660 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: Physical Metrics of Kidney and Spleen Destination: subsection.2.1 Item: Title: Histopathological Assessment: H&E and Congo Red Staining Destination: subsection.2.2 Item: Title: Oxidative Stress Status Destination: subsection.2.3 Item: Title: Statistical Correlation between the Studied Variables Destination: subsection.2.4 Item: Title: Discussion Destination: section.3 Children: Item: Title: Physical and Histopathological Alterations of Kidney and Spleen Destination: subsection.3.1 Item: Title: Kidney and Spleen Oxidative Stress Destination: subsection.3.2 Item: Title: Correlations between Behavior, Histopathology, HPA Axis and Peripheral Oxidative Stress Destination: subsection.3.3 Item: Title: Study Limitations Destination: subsection.3.4 Item: Title: Future Perspective of Peripheral Organs in AD Destination: subsection.3.5 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: Physical Status Destination: subsection.4.3 Item: Title: Behavioral Phenotype Destination: subsection.4.4 Item: Title: Histopathological Assessment Destination: subsection.4.5 Children: Item: Title: Morphological and Structural Analysis with H&E Destination: subsubsection.4.5.1 Item: Title: Congo Red Staining for Amyloidosis Destination: subsubsection.4.5.2 Item: Title: Oxidative Stress Analysis Destination: subsection.4.6 Item: Title: Functional Correlates Destination: subsection.4.7 Item: Title: Statistics Destination: subsection.4.8 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: section.6 Info: Title: Glomerular Hypertrophy and Splenic Red Pulp Degeneration Concurrent with Oxidative Stress in 3xTg-AD Mice Model for Alzheimer’s Disease and Its Exacerbation with Sex and Social Isolation Author: Juan Fraile-Ramos, Josep Reig-Vilallonga and Lydia Giménez-Llort Subject: The continuously expanding field of Alzheimer’s disease (AD) research is now beginning to defocus the brain to take a more systemic approach to the disease, as alterations in the peripheral organs could be related to disease progression. One emerging hypothesis is organ involvement in the process of A clearance. In the present work, we aimed to examine the status and involvement of the kidney as a key organ for waste elimination and the spleen, which is in charge of filtering the blood and producing lymphocytes, and their influence on AD. The results showed morphological and structural changes due to acute amyloidosis in the kidney (glomeruli area) and spleen (red pulp area and red/white pulp ratio) together with reduced antioxidant defense activity (GPx) in 16-month-old male and female 3xTg-AD mice when compared to their age- and sex-matched non-transgenic (NTg) counterparts. All these alterations correlated with the anxious-like behavioral phenotype of this mouse model. In addition, forced isolation, a cause of psychological stress, had a negative effect by intensifying genotype differences and causing differences to appear in NTg animals. This study further supports the relevance of a more integrative view of the complex interplay between systems in aging, especially at advanced stages of Alzheimer’s disease. 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