Language

English

Publication Date

9-30-2026

Journal

Science Bulletin

DOI

10.1016/j.scib.2026.08.057

PMID

42686501

Abstract

Normal estrogen exposure, as observed in eumenorrheic women of reproductive age, is important for neurocognition, as demonstrated by postmenopausal hormone replacement. However, the cognitive effects of sustained high-level estrogen in the context of oral contraceptives or pregnancy are unclear. Here, we show that high estrogen induces temporary memory dysfunction in mice without affecting mood-related behaviors or exploratory motivation, which is associated with altered gene expression in the lateral hypothalamus (LH). Depletion of neuronal estrogen receptor α/β (ERα/β) in the LH rescues estrogen- or pregnancy-induced cognitive dysfunction. Single-nucleus RNA-seq revealed that ERα, the predominant ER in the LH, is enriched in Gamma-Aminobutyric Acid-releasing (GABAergic) neurons and that high-level estrogen downregulates GABA-A receptor signaling within LH

Keywords

Animals, Female, Estrogens, Signal Transduction, Pregnancy, Mice, Estrogen Receptor alpha, Memory Disorders, Memory, Hippocampus, Hypothalamus, Estrogen Receptor beta, GABAergic Neurons, Mice, Inbred C57BL, Receptors, Estrogen, Estrogen, Hypothalamus, Memory, Momnesia, Pregnancy brain

Published Open-Access

yes

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