Ovariectomy and High Fat-Sugar-Salt Diet Induced Alzheimer's Disease/Vascular Dementia Features in Mice.

Autor: Sweetat S; Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah Hebrew University Medical Center, Jerusalem, Israel.; Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel. Hadassah BrainLabs-National Knowledge Center for Research on Brain Diseases, Hadassah-Hebrew University Medical Center, Jerusalem Israel., Shabat MB; Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah Hebrew University Medical Center, Jerusalem, Israel.; Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel. Hadassah BrainLabs-National Knowledge Center for Research on Brain Diseases, Hadassah-Hebrew University Medical Center, Jerusalem Israel., Theotokis P; Department of Neurology, AHEPA University Hospital, Aristotle University of Thessaloniki, Greece., Suissa N; Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah Hebrew University Medical Center, Jerusalem, Israel.; Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel. Hadassah BrainLabs-National Knowledge Center for Research on Brain Diseases, Hadassah-Hebrew University Medical Center, Jerusalem Israel., Karafoulidou E; Department of Neurology, AHEPA University Hospital, Aristotle University of Thessaloniki, Greece., Touloumi O; Department of Neurology, AHEPA University Hospital, Aristotle University of Thessaloniki, Greece., Abu-Fanne R; Department of Clinical Biochemistry, Hadassah Hebrew University Medical Center, Jerusalem, Israel., Abramsky O; Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah Hebrew University Medical Center, Jerusalem, Israel., Wolf G; Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel. Hadassah BrainLabs-National Knowledge Center for Research on Brain Diseases, Hadassah-Hebrew University Medical Center, Jerusalem Israel.; Biological Psychiatry Laboratory, Hadassah Hebrew University Medical Center, Jerusalem Israel Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.; Department of Psychology, School of Psychology and Social Sciences, Achva Academic College, Be'er Tuvia, Israel., Saada A; Department of Genetics, Hadassah Hebrew University Medical Center, Jerusalem, Israel; Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel., Lotan A; Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel. Hadassah BrainLabs-National Knowledge Center for Research on Brain Diseases, Hadassah-Hebrew University Medical Center, Jerusalem Israel.; Biological Psychiatry Laboratory, Hadassah Hebrew University Medical Center, Jerusalem Israel Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel., Grigoriadis N; Department of Neurology, AHEPA University Hospital, Aristotle University of Thessaloniki, Greece., Rosenmann H; Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah Hebrew University Medical Center, Jerusalem, Israel.; Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel. Hadassah BrainLabs-National Knowledge Center for Research on Brain Diseases, Hadassah-Hebrew University Medical Center, Jerusalem Israel.
Jazyk: angličtina
Zdroj: Aging and disease [Aging Dis] 2024 Oct 01; Vol. 15 (5), pp. 2284-2300. Date of Electronic Publication: 2024 Oct 01.
DOI: 10.14336/AD.2024.03110
Abstrakt: While the vast majority of Alzheimer's disease (AD) is non-familial, the animal models of AD that are commonly used for studying disease pathogenesis and development of therapy are mostly of a familial form. We aimed to generate a model reminiscent of the etiologies related to the common late-onset Alzheimer's disease (LOAD) sporadic disease that will recapitulate AD/dementia features. Naïve female mice underwent ovariectomy (OVX) to accelerate aging/menopause and were fed a high fat-sugar-salt diet to expose them to factors associated with increased risk of development of dementia/AD. The OVX mice fed a high fat-sugar-salt diet responded by dysregulation of glucose/insulin, lipid, and liver function homeostasis and increased body weight with slightly increased blood pressure. These mice developed AD-brain pathology (amyloid and tangle pathologies), gliosis (increased burden of astrocytes and activated microglia), impaied blood vessel density and neoangiogenesis, with cognitive impairment. Thus, OVX mice fed on a high fat-sugar-salt diet imitate a non-familial sporadic/environmental form of AD/dementia with vascular damage. This model is reminiscent of the etiologies related to the LOAD sporadic disease that represents a high portion of AD patients, with an added value of presenting concomitantly AD and vascular pathology, which is a common condition in dementia. Our model can, thereby, provide a valuable tool for studying disease pathogenesis and for the development of therapeutic approaches.
Databáze: MEDLINE