TY - JOUR
T1 - 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
AU - Kara, Firat
AU - Belloy, Michael E.
AU - Voncken, Rick
AU - Sarwari, Zahra
AU - Garima, Yadav
AU - Anckaerts, Cynthia
AU - Langbeen, An
AU - Leysen, Valerie
AU - Shah, Disha
AU - Jacobs, Jules
AU - Hamaide, Julie
AU - Bols, Peter
AU - Van Audekerke, Johan
AU - Daans, Jasmijn
AU - Guglielmetti, Caroline
AU - Kantarci, Kejal
AU - Prevot, Vincent
AU - Roßner, Steffen
AU - Ponsaerts, Peter
AU - Van der Linden, Annemie
AU - Verhoye, Marleen
N1 - Funding Information:
We thank to Dr. Elisabeth Jonckers for her support for data analysis. The computational resources and services used in this work were provided by the HPC core facility CalcUA of the Universiteit Antwerpen, the VSC (Flemish Supercomputer Center), funded by the Hercules Foundation and the Flemish Government – department EWI. This research was supported by the European Union's Seventh Framework Program under grant agreement number 278850 (INMiND), the Fund for Scientific Research Flanders (FWO) (grant agreements G057615N and 12S4815N), the Stichting Alzheimer Onderzoek (SAO-FRA, grant agreement 13026), the interdisciplinary PhD grant BOF DOCPRO 2014 (granted to MV), by a KP-BOF 2015 from the University of Antwerp (granted to FK) and by the Agence Nationale de la Recherche (ANR GRAND, ANR-17-CE16-0015-01 to VP). The 9.4T Bruker MR system was in part funded by the Flemish Impulse funding for heavy scientific equipment (42/FA010100/123) granted to Prof. Dr Annemie Van der Linden.
Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2021/6
Y1 - 2021/6
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - Astrocytes
KW - Diffusion Tensor Imaging
KW - Tg2576 mice
KW - amyloid-beta (Aβ)
KW - functional connectivity
KW - human APP Swedish
KW - magnetic resonance spectroscopy
KW - ovarian hormones
KW - ovariectomy
KW - resting state fMRI
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U2 - 10.1016/j.neurobiolaging.2021.02.011
DO - 10.1016/j.neurobiolaging.2021.02.011
M3 - Article
C2 - 33765427
AN - SCOPUS:85103068212
SN - 0197-4580
VL - 102
SP - 139
EP - 150
JO - Neurobiology of aging
JF - Neurobiology of aging
ER -