41670b3bca872efa5afb5e5da161844e blsf-19-00005.pdf 75f44e415237a566c39d93c6a47475adc33138b8 blsf-19-00005.pdf 26b67bac03521081bd308c40c66b3a5bcc5af2549b48080f709fd030f4a90a1c blsf-19-00005.pdf Title: Sex-Dependent Variations in Voluntary Exercise of 14-Month-Old 3xTg-AD Mice Associated with Novelty Inhibition "2279 Subject: Alzheimer’s Disease (AD) patients suffer from circadian rhythm alterations involving sleep, thermoregulation, and movement activity disorders. The latter affects their daily patterns of physical activity (PA) and willingness to perform voluntary exercise, impeding benefit from routine PA practice. Neuropsychiatric symptoms (NPS) have been postulated to influence human physical activity engagement. However, there is no clarity on whether animal models can replicate these effects. Herein, we evaluated the behavioral circadian rhythmicity of voluntary physical exercise (VPE) in a group of 14-month-old 3xTg-AD animals of both sexes at advanced stages of the disease and compared their performance according to the presence of NPS-like symptoms. Mice (n = 9 females and n = 7 males) were provided with an in-cage running wheel for 30 days with daily control of the diurnal and nocturnal amount of VPE performed. Using a Linear Mixed Model Analysis, we found that all animals kept similar nocturnal patterns of VPE. However, sex-dependent differences associated with previous novelty inhibition (NI) response, an NPS-like symptom frequently observed in this model, were found during diurnal periods. Thus, males with high NI showed significantly higher levels of VPE compared with high NI females. No sex differences were found in low NI animals. Our results suggest that the influence of NPS-like symptoms in VPA engagement may vary depending on the sex of 3xTg-AD mice. Further studies are needed to help us to elucidate molecular and genetic factors associated with these differences. Keywords: Alzheimer disease; mice; animal model; sex difference; running; exercise Author: Daniel Alveal-Mellado and Lydia Giménez-Llort Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Wed Nov 23 08:47:56 2022 CET ModDate: Wed Nov 23 09:08:35 2022 CET Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 3 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 231526 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 LZJWOX+VnURWPalladioL Type 1 Custom yes yes no 15 0 AGVXRC+URWPalladioL-Bold Type 1 Custom yes yes no 19 0 SEOZHF+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 EKXBQH+URWPalladioL-Ital Type 1 Custom yes yes no 28 0 DVCMRV+CMSY10 Type 1 Builtin yes yes no 76 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2025-02-20 02:15:02 CET RepresentationInformation: blsf-19-00005.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2025-02-19 10:18:21 CET Size: 231526 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 122 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Item: Title: Results Destination: section.3 Item: Title: Conclusions Destination: section.4 Item: Title: References Destination: section.4 Info: Title: Sex-Dependent Variations in Voluntary Exercise of 14-Month-Old 3xTg-AD Mice Associated with Novelty Inhibition "2279 Author: Daniel Alveal-Mellado and Lydia Giménez-Llort Subject: Alzheimer’s Disease (AD) patients suffer from circadian rhythm alterations involving sleep, thermoregulation, and movement activity disorders. The latter affects their daily patterns of physical activity (PA) and willingness to perform voluntary exercise, impeding benefit from routine PA practice. Neuropsychiatric symptoms (NPS) have been postulated to influence human physical activity engagement. However, there is no clarity on whether animal models can replicate these effects. Herein, we evaluated the behavioral circadian rhythmicity of voluntary physical exercise (VPE) in a group of 14-month-old 3xTg-AD animals of both sexes at advanced stages of the disease and compared their performance according to the presence of NPS-like symptoms. Mice (n = 9 females and n = 7 males) were provided with an in-cage running wheel for 30 days with daily control of the diurnal and nocturnal amount of VPE performed. Using a Linear Mixed Model Analysis, we found that all animals kept similar nocturnal patterns of VPE. However, sex-dependent differences associated with previous novelty inhibition (NI) response, an NPS-like symptom frequently observed in this model, were found during diurnal periods. Thus, males with high NI showed significantly higher levels of VPE compared with high NI females. No sex differences were found in low NI animals. Our results suggest that the influence of NPS-like symptoms in VPA engagement may vary depending on the sex of 3xTg-AD mice. Further studies are needed to help us to elucidate molecular and genetic factors associated with these differences. 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