301e52350a6498a872a3351ff99e1006 msf-08-00008.pdf 9ac8be55f860ecfec4a2321b8292353eb53829c6 msf-08-00008.pdf 6bad91a58900484ac8e3e6e3e55e62e4a07546506e553c5f9eeab030494b406e msf-08-00008.pdf Title: Sex-Dependent Hepatomegaly, and Increased Hepatic Oxidative Stress in Old Male and Female 3xTg-AD Mice as Compared to Mice with Physiological Aging "2279 Subject: When it comes to neurodegenerative disorders, Alzheimer’s disease (AD) is one of the main causes of dementia in older people. Until now, studies have focused on alterations occurring in the brain. However, it has been shown that along with the accumulation of beta-amyloid plaques and tau proteins, oxidative stress and inflammation also play a role in this disease’s pathophysiology. Peripheral organs such as the liver, the central organ regulating metabolism and supporting the immune system, could affect AD pathophysiological development and/or progress. We have previously described hepatic oxidative stress in 6-month-old 3xTg-AD mice, an age mimicking the prodromal stages of AD disease. In the present work, we studied the impact of AD-genotype and sex effects on liver dysfunction in 16-month-old male and female 3xTg-AD mice, an age mimicking advanced neuropathological stages of the disease, and as compared to age- and sex-matched non-transgenic mice with physiological aging. The mass index results showed hepatic damage as hepatomegaly in 3xTg-AD mice. A sex-dependent increase in hepatic tissue oxidative stress, measured through antioxidant enzymes glutathione reductase (Gr) and glutathione peroxidase (Gpx), and antioxidant compound glutathione (GSH), was found in 3xTg-AD mice. Furthermore, the correlations between the enzymes and the hepatic index also showed sex and genotype differences. These results indicate that liver status is affected in 3xTg-AD mice; it is affected in a sexually differential manner and could favor AD progression. Further ongoing analysis regarding -amyloid and lipidic depositions on the liver would determine if these alterations correlate with a worse prognosis of the disease. Keywords: Alzheimer’s disease; aging; peripheral organs; liver; oxidative stress; sex differences Author: Juan Fraile-Ramos and Lydia Giménez-Llort Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Thu Aug 4 13:05:13 2022 CEST ModDate: Thu Aug 4 13:16:17 2022 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 2 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 222157 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- BTFGED+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 OYGWHX+VnURWPalladioL Type 1 Custom yes yes no 15 0 LWLIVD+EURM10 Type 1 Builtin yes yes no 19 0 INFDZE+URWPalladioL-Bold Type 1 Custom yes yes no 23 0 UJJGMI+URWPalladioL-Roma Type 1 Custom yes yes no 28 0 RSRADC+URWPalladioL-Ital Type 1 Custom yes yes no 32 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2025-02-20 02:15:51 CET RepresentationInformation: msf-08-00008.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2025-02-19 10:18:54 CET Size: 222157 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 110 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: References Destination: Doc-Start Info: Title: Sex-Dependent Hepatomegaly, and Increased Hepatic Oxidative Stress in Old Male and Female 3xTg-AD Mice as Compared to Mice with Physiological Aging "2279 Author: Juan Fraile-Ramos and Lydia Giménez-Llort Subject: When it comes to neurodegenerative disorders, Alzheimer’s disease (AD) is one of the main causes of dementia in older people. Until now, studies have focused on alterations occurring in the brain. However, it has been shown that along with the accumulation of beta-amyloid plaques and tau proteins, oxidative stress and inflammation also play a role in this disease’s pathophysiology. Peripheral organs such as the liver, the central organ regulating metabolism and supporting the immune system, could affect AD pathophysiological development and/or progress. We have previously described hepatic oxidative stress in 6-month-old 3xTg-AD mice, an age mimicking the prodromal stages of AD disease. In the present work, we studied the impact of AD-genotype and sex effects on liver dysfunction in 16-month-old male and female 3xTg-AD mice, an age mimicking advanced neuropathological stages of the disease, and as compared to age- and sex-matched non-transgenic mice with physiological aging. The mass index results showed hepatic damage as hepatomegaly in 3xTg-AD mice. A sex-dependent increase in hepatic tissue oxidative stress, measured through antioxidant enzymes glutathione reductase (Gr) and glutathione peroxidase (Gpx), and antioxidant compound glutathione (GSH), was found in 3xTg-AD mice. Furthermore, the correlations between the enzymes and the hepatic index also showed sex and genotype differences. These results indicate that liver status is affected in 3xTg-AD mice; it is affected in a sexually differential manner and could favor AD progression. Further ongoing analysis regarding -amyloid and lipidic depositions on the liver would determine if these alterations correlate with a worse prognosis of the disease. 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