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 - 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
UR - http://www.scopus.com/inward/record.url?scp=85103068212&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85103068212&partnerID=8YFLogxK
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 -