1. Long-term ovarian hormone deprivation alters functional connectivity, brain neurochemical profile and white matter integrity in the Tg2576 amyloid mouse model of Alzheimer's disease.
- Author
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Kara F, Belloy ME, Voncken R, Sarwari Z, Garima Y, Anckaerts C, Langbeen A, Leysen V, Shah D, Jacobs J, Hamaide J, Bols P, Van Audekerke J, Daans J, Guglielmetti C, Kantarci K, Prevot V, Roßner S, Ponsaerts P, Van der Linden A, and Verhoye M
- Subjects
- Alzheimer Disease etiology, Alzheimer Disease genetics, Animals, Biomarkers, Disease Models, Animal, Genotype, Magnetic Resonance Imaging, Mice, Inbred C57BL, Mice, Transgenic, Placebos, Risk Factors, Time Factors, White Matter diagnostic imaging, Mice, Alzheimer Disease diagnostic imaging, Alzheimer Disease psychology, Brain Chemistry, Executive Function, Ovariectomy adverse effects, White Matter metabolism, White Matter physiopathology
- Abstract
Premenopausal bilateral ovariectomy is considered to be one of the risk factors of Alzheimer's disease (AD). However, the underlying mechanisms remain unclear. Here, we aimed to investigate long-term neurological consequences of ovariectomy in a rodent AD model, TG2576 (TG), and wild-type mice (WT) that underwent an ovariectomy or sham-operation, using in vivo MRI biomarkers. An increase in osmoregulation and energy metabolism biomarkers in the hypothalamus, a decrease in white matter integrity, and a decrease in the resting-state functional connectivity was observed in ovariectomized TG mice compared to sham-operated TG mice. In addition, we observed an increase in functional connectivity in ovariectomized WT mice compared to sham-operated WT mice. Furthermore, genotype (TG vs. WT) effects on imaging markers and GFAP immunoreactivity levels were observed, but there was no effect of interaction (Genotype × Surgery) on amyloid-beta-and GFAP immunoreactivity levels. Taken together, our results indicated that both genotype and ovariectomy alters imaging biomarkers associated with AD., Competing Interests: Declaration of competing interest None., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2021
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