Loss of ovarian function and estrogen therapy remodel the brain's synaptic and metabolic proteome

American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 2026 Open access

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Authors: Sebastian F. Salathe, Edziu Franczak, Zane Busick, Frederick B. Boakye, Julie Allen, Andrew J. Lutkewitte, Heather Wilkins, John P. Thyfault, Benjamin A. Kugler
DOI: 10.1152/ajpregu.00031.2026
Cited by: 1
References: 48

Abstract

The menopausal transition, marked by declining estrogen levels, alters cognition, neuroplasticity, and brain metabolism. Although hormone therapy benefits cognition, its molecular effects on the brain remain unclear. Using whole-brain proteomics in aged ovariectomized (OVX) mice with or without estrogen treatment, we found that OVX reduced proteins linked to synaptogenesis and mitochondrial metabolism. Estrogen reversed these declines, restoring pathways supporting neuronal signaling and energy balance, identifying estrogen-regulated proteins critical for maintaining brain health during menopause.

Fields of Study & Subjects

Menopause: Health Impacts and Treatments Cancer-related cognitive impairment studies Estrogen and related hormone effects

Publication details

Journal / source
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
Publisher
American Physiological Society
Volume
330
Issue
5
Pages
R489–R500
Publication date
2 April 2026
Language
EN