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

Firat Kara, Michael E. Belloy, Rick Voncken, Zahra Sarwari, Yadav Garima, Cynthia Anckaerts, An Langbeen, Valerie Leysen, Disha Shah, Jules Jacobs, Julie Hamaide, Peter Bols, Johan Van Audekerke, Jasmijn Daans, Caroline Guglielmetti, Kejal Kantarci, Vincent Prevot, Steffen Roßner, Peter Ponsaerts, Annemie Van der LindenMarleen Verhoye

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)139-150
Number of pages12
JournalNeurobiology of aging
Volume102
DOIs
StatePublished - Jun 2021

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

Fingerprint Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this