3776a408d585203eda43efa9709345a0 biomedicines_a2021v9n2p111.pdf e09c6f62b9f20a56c3c5ff742bc4038b23f878ad biomedicines_a2021v9n2p111.pdf 2de6b386de26640c6c343cc1090885950fe77430ac6b0024179a3d171f44e373 biomedicines_a2021v9n2p111.pdf Title: Sex-Dependent End-of-Life Mental and Vascular Scenarios for Compensatory Mechanisms in Mice with Normal and AD-Neurodegenerative Aging Subject: Life expectancy decreases with aging, with cardiovascular, mental health, and neurodegenerative disorders strongly contributing to the total disability-adjusted life years. Interestingly, the morbidity/mortality paradox points to females having a worse healthy life expectancy. Since bidirectional interactions between cardiovascular and Alzheimer’s diseases (AD) have been reported, the study of this emerging field is promising. In the present work, we further explored the cardiovascular–brain interactions in mice survivors of two cohorts of non-transgenic and 3xTg-AD mice, including both sexes, to investigate the frailty/survival through their life span. Survival, monitored from birth, showed exceptionally worse mortality rates in females than males, independently of the genotype. This mortality selection provided a “survivors” cohort that could unveil brain–cardiovascular interaction mechanisms relevant for normal and neurodegenerative aging processes restricted to long-lived animals. The results show sex-dependent distinct physical (worse in 3xTg-AD males), neuropsychiatric-like and cognitive phenotypes (worse in 3xTg-AD females), and hypothalamic–pituitary–adrenal (HPA) axis activation (higher in females), with higher cerebral blood flow and improved cardiovascular phenotype in 3xTg-AD female mice survivors. The present study provides an experimental scenario to study the suggested potential compensatory hemodynamic mechanisms in end-of-life dementia, which is sex-dependent and can be a target for pharmacological and non-pharmacological interventions. Keywords: healthy life expectancy (HALE); morbidity/mortality paradox; anxiety; cognition; systolic blood pressure; cerebral blood flow; arterial properties; angiogenesis; gender medicine; neurodegenerative disorders Author: Aida Muntsant, Francesc Jiménez-Altayó, Lidia Puertas-Umbert, Elena Jiménez-Xarrie, Elisabet Vila and Lydia Giménez-Llort Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Tue Jan 26 03:43:23 2021 CET ModDate: Tue Jan 26 03:56:30 2021 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 29 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 5412944 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- HJOMHV+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 OHKNFJ+VnURWPalladioL Type 1 Custom yes yes no 15 0 NTEJPX+URWPalladioL-Ital Type 1 Custom yes yes no 19 0 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edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1b26f7b2 Item: Title: Angiogenesis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@491cc5c9 Item: Title: Arterial Properties Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@74ad1f1f Item: Title: Mental Health and Cardiovascular Function Correlates Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6a1aab78 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@462d5aee Children: Item: Title: Sex- and Genotype-Dependent Mortality/Morbidity Paradox Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@69b0fd6f Item: Title: Down-Regulation of HPA Axis Endocrine Status in Female 3xTg-AD Mice Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@757942a1 Item: Title: Different Behavioral Signatures for Physical, Emotional, and Cognitive Phenotypes Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4a87761d Item: Title: Increased MRI-ASL Regional Cerebral Blood Flow in 3xTg-AD Survivor Females Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@66d1af89 Item: Title: Sex- and Brain-Region-Dependent Asymmetry in the MRI-ASL Regional Cerebral Blood Flow Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@8646db9 Item: Title: Improved Vascular Profile in 3xTg-AD Survivor Females Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@37374a5e Item: Title: Behavioral Correlates Mental Health and Cardiovascular Measurements Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4671e53b Item: Title: Future Research Directions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@2db7a79b Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6950e31 Info: Title: Sex-Dependent End-of-Life Mental and Vascular Scenarios for Compensatory Mechanisms in Mice with Normal and AD-Neurodegenerative Aging Author: Aida Muntsant, Francesc Jiménez-Altayó, Lidia Puertas-Umbert, Elena Jiménez-Xarrie, Elisabet Vila and Lydia Giménez-Llort Subject: Life expectancy decreases with aging, with cardiovascular, mental health, and neurodegenerative disorders strongly contributing to the total disability-adjusted life years. Interestingly, the morbidity/mortality paradox points to females having a worse healthy life expectancy. Since bidirectional interactions between cardiovascular and Alzheimer’s diseases (AD) have been reported, the study of this emerging field is promising. In the present work, we further explored the cardiovascular brain interactions in mice survivors of two cohorts of non-transgenic and 3xTg-AD mice, including both sexes, to investigate the frailty/survival through their life span. Survival, monitored from birth, showed exceptionally worse mortality rates in females than males, independently of the genotype. This mortality selection provided a “survivors” cohort that could unveil brain cardiovascular interaction mechanisms relevant for normal and neurodegenerative aging processes restricted to long-lived animals. The results show sex-dependent distinct physical (worse in 3xTg-AD males), neuropsychiatric-like and cognitive phenotypes (worse in 3xTg-AD females), and hypothalamic pituitary adrenal (HPA) axis activation (higher in females), with higher cerebral blood flow and improved cardiovascular phenotype in 3xTg-AD female mice survivors. The present study provides an experimental scenario to study the suggested potential compensatory hemodynamic mechanisms in end-of-life dementia, which is sex-dependent and can be a target for pharmacological and non-pharmacological interventions. 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