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

NEUROBIOLOGY OF AGING

卷:102

Article

Kara, Firat¹  Belloy, Michael E.¹  Voncken, Rick¹  Sarwari, Zahra¹  Garima, Yadav¹  Anckaerts, Cynthia¹  Langbeen, An²  Leysen, Valerie³  Shah, Disha¹  Jacobs, Jules⁷  Hamaide, Julie¹  Bols, Peter²  Van Audekerke, Johan¹  Daans, Jasmijn⁴  Guglielmetti, Caroline⁸  Kantarci, Kejal⁵  Prevot, Vincent³  Rossner, Steffen⁶  Ponsaerts, Peter⁴  Van der Linden, Annemie¹  Verhoye, Marleen¹ 

[1] Univ Antwerp, Dept Biomed Sci, Bioimaging Lab, INMIND Consortium, Univ Pl 1, B-2610 Antwerp, Belgium

[2] Univ Antwerp, Dept Vet Sci, Vet Physiol & Biochem, Antwerp, Belgium

[3] Univ Lille, Inserm, CHU Lille,UMR S1172,DistalZ, Dev & Plast Neuroendocrine Brain,Lille Neurosci &, Lille, France

[4] Univ Antwerp, Vaccine & Infect Dis Inst Vaxinfectio, Lab Expt Hematol, Antwerp, Belgium

[5] Mayo Clin, Dept Radiol, Rochester, MN USA

[6] Univ Leipzig, Paul Flechsig Inst Brain Res, Leipzig, Germany

[7] Univ Nijmegen, Nijmegen, Netherlands

[8] Univ Calif San Francisco, San Francisco, CA 94143 USA

关键词: Alzheimer's disease;    amyloid-beta (A beta);    functional connectivity;    resting state fMRI;    magnetic resonance spectroscopy;    Diffusion Tensor Imaging;    ovariectomy ovarian hormones;    Tg2576 mice;    human APP Swedish;    Astrocytes;   

DOI  :  10.1016/j.neurobiolaging.2021.02.011

来源: Elsevier

【 摘 要 】

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 xSurgery) on amyloid-beta-and GFAP immunoreactivity levels. Taken together, our results indicated that both genotype and ovariectomy alters imaging biomarkers associated with AD. (C) 2021 Elsevier Inc. All rights reserved.

【 授权许可】

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