Loss of ovarian function and estrogen therapy remodel the brain's synaptic and metabolic proteome
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.
Authors
- Benjamin A. Kugler (ORCID: https://orcid.org/0000-0003-0822-7106)
- Andrew J. Lutkewitte (ORCID: https://orcid.org/0000-0001-7271-246X)
- Edziu Franczak (ORCID: https://orcid.org/0000-0002-0845-4002)
- Heather Wilkins (ORCID: https://orcid.org/0000-0003-4563-4544)
- John P. Thyfault (ORCID: https://orcid.org/0000-0001-7920-7466)
- Julie Allen
- Sebastian F. Salathe
- Zane Busick
- Frederick B. Boakye
Institutions
- Texas Diabetes Institute (US)
- University of Kansas Medical Center (US)
Publication Details
- Journal
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
- Published
- 2026-04-02
- DOI
- https://doi.org/10.1152/ajpregu.00031.2026
- Primary Topic
- Menopause: Health Impacts and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- U.S. Department of Veterans Affairs
- National Institute on Aging
- National Institute of Diabetes and Digestive and Kidney Diseases
- Division of Diabetes, Endocrinology, and Metabolic Diseases