76b46f0fc7183de6b3429d9e364673e9 biomedicines_a2021v9n8p994.pdf 3c8a4c07c582b5007a673ad39c2dbd64d81408c2 biomedicines_a2021v9n8p994.pdf 9b3b7503a26849c5519105c2f5f330b60658ac35b84d18cbd79321e58941b13e biomedicines_a2021v9n8p994.pdf Title: Sex-Dependent Signatures, Time Frames and Longitudinal Fine-Tuning of the Marble Burying Test in Normal and AD-Pathological Aging Mice Subject: The marble burying (MB) test, a classical test based on the natural tendency of rodents to dig in diverse substrates and to bury small objects, is sensitive to some intrinsic and extrinsic factors. Here, under emerging neuroethological quantitative and qualitative analysis, the MB performance of 12-month-old male and female 3xTg-AD mice for Alzheimer’s disease and age-matched counterparts of gold-standard C57BL6 strain with normal aging unveiled sex-dependent signatures. In addition, three temporal analyses, through the (1) time course of the performance, and (2) a repeated test schedule, identified the optimal time frames and schedules to detect sex- and genotype-dependent differences. Besides, a (3) longitudinal design from 12 to 16 months of age monitored the changes in the performance with aging, worsening in AD-mice, and modulation through the repeated test. In summary, the present results allow us to conclude that (1) the marble burying test is responsive to genotype, sex, aging, and its interactions; (2) the male sex was more sensitive to showing the AD-phenotype; (3) longitudinal assessment shows a reduction in females with AD pathology; (4) burying remains stable in repeated testing; (5) the time-course of marbles burying is useful; and (6) burying behavior most likely represents perseverative and/or stereotyped-like behavior rather than anxiety-like behavior in 3xTg-AD mice. Keywords: neuroethology; behavioral neuroscience methodology; sexual differences; aging; Alzheimer’s disease; comorbidities; phobia; anxiety; OCD (obsessive-compulsive symptoms) Author: Mikel Santana-Santana, José-Ramón Bayascas and Lydia Giménez-Llort Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Wed Aug 11 12:24:51 2021 CEST ModDate: Wed Aug 11 12:28:56 2021 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 16 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1167260 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- HCBGQO+VnURWPalladioL Type 1 Custom yes yes no 10 0 LAHQNJ+URWPalladioL-Ital Type 1 Custom yes yes no 15 0 HHMSEQ+URWPalladioL-Bold Type 1 Custom yes yes no 20 0 KLXHNV+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 HJOMHV+VnURWPalladioL-Bold Type 1 Custom yes yes no 28 0 EBFBTV+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 36 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 58 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 62 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 66 0 OJYQXC+CMSY10 Type 1 Builtin yes yes no 81 0 LWLIVD+EURM10 Type 1 Builtin yes yes no 85 0 HDHAMO+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 92 0 HDHAMP+PalatinoLinotype CID TrueType Identity-H yes yes yes 95 0 HDHANA+PalatinoLinotype TrueType WinAnsi yes yes no 101 0 HDHANC+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 104 0 HDHAMO+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 117 0 HDHANA+PalatinoLinotype TrueType WinAnsi yes yes no 120 0 HDHANC+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 123 0 HDHAMO+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 139 0 HDHANA+PalatinoLinotype TrueType WinAnsi yes yes no 142 0 HDHANC+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 145 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2022-03-12 02:27:29 CET RepresentationInformation: biomedicines_a2021v9n8p994.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2022-03-10 11:44:46 CET Size: 1167260 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 380 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Children: Item: Title: Animals Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Experimental Design Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Behavioral Assessments Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Statistics Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Children: Item: Title: Corner Test for Neophobia Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Longitudinal Assessment of Marble Burying Test and Repeated Test Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Corner Test and Marble Burying Test Correlations Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Children: Item: Title: New Insight of Burying Behavior in 3xTg-AD Mice Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: Corner Test and Its Relationship with Marble Burying Test in 3xTg-AD Mice Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: Marble Test as a Model of Anxiety-Like or OCD-Like Behavior in 3xTg-AD Mice? Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: Integrating Our New Findings into Our Previous Knowledge of The Burying Behavior of 3xTg-AD Mice Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Item: Title: Benefits of Implementing the Time-Course of Marble Buried Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Item: Title: Methodological Limitations of the Study Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@76a3e297 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4d3167f4 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@ed9d034 Info: Title: Sex-Dependent Signatures, Time Frames and Longitudinal Fine-Tuning of the Marble Burying Test in Normal and AD-Pathological Aging Mice Author: Mikel Santana-Santana, José-Ramón Bayascas and Lydia Giménez-Llort Subject: The marble burying (MB) test, a classical test based on the natural tendency of rodents to dig in diverse substrates and to bury small objects, is sensitive to some intrinsic and extrinsic factors. Here, under emerging neuroethological quantitative and qualitative analysis, the MB performance of 12-month-old male and female 3xTg-AD mice for Alzheimer’s disease and age-matched counterparts of gold-standard C57BL6 strain with normal aging unveiled sex-dependent signatures. In addition, three temporal analyses, through the (1) time course of the performance, and (2) a repeated test schedule, identified the optimal time frames and schedules to detect sex- and genotype-dependent differences. Besides, a (3) longitudinal design from 12 to 16 months of age monitored the changes in the performance with aging, worsening in AD-mice, and modulation through the repeated test. In summary, the present results allow us to conclude that (1) the marble burying test is responsive to genotype, sex, aging, and its interactions; (2) the male sex was more sensitive to showing the AD-phenotype; (3) longitudinal assessment shows a reduction in females with AD pathology; (4) burying remains stable in repeated testing; (5) the time-course of marbles burying is useful; and (6) burying behavior most likely represents perseverative and/or stereotyped-like behavior rather than anxiety-like behavior in 3xTg-AD mice. 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