2026-02-03 カリフォルニア大学アーバイン校(UCI)
<関連情報>
- https://news.uci.edu/2026/02/03/high-estrogen-levels-in-brain-may-increase-womens-risk-of-stress-related-memory-issues/
- https://www.cell.com/neuron/fulltext/S0896-6273(25)00993-6
海馬のエストロゲンレベル、受容体の種類、エピジェネティクスは、同時発生の急性ストレスに対する性別特有の記憶の脆弱性に寄与する Hippocampal estrogen levels, receptor types, and epigenetics contribute to sex-specific memory vulnerabilities to concurrent acute stresses
Rachael E. Hokenson ∙ Kiara L. Rodríguez-Acevedo ∙ Yuncai Chen ∙ … ∙ Kiran K. Soma ∙ Elizabeth A. Heller ∙ Tallie Z. Baram
Neuron Published:February 3, 2026
DOI:https://doi.org/10.1016/j.neuron.2025.12.037
Graphical abstract
Highlights
- Acute concurrent stresses provoke long-lasting, sex-specific memory problems
- Stress vulnerability requires high physiological hippocampal estrogen levels
- High estrogen levels generate a permissive chromatin, enabling plasticity
- Stress-induced maladaptive memory plasticity involves ERα in males and ERβ in females
Summary
It is increasingly recognized that acute traumatic events (e.g., mass shootings, natural disasters) can provoke enduring episodic memory deficits and generalization of trauma cues, and these are more common in women. We investigated the mechanisms and sex differences in memory vulnerability to multiple acute concurrent stresses (MACSs) in mice, focusing on the sex hormone 17β-estradiol and its receptors in the hippocampus. Surprisingly, high physiological hippocampal estradiol levels, observed in proestrus females and males, were required for MACS-induced episodic memory disruption and sensitization and generalization of stress cues. High estradiol levels were associated with permissive chromatin states in stress-vulnerable mice, while chromatin permissiveness and hippocampal estradiol were low in stress-resilient estrus females. Estrogen receptor (ER)β activation in resilient estrus females increased chromatin permissiveness and enduring vulnerability to MACSs, while ERα mediated milder stress-induced memory disruptions in males. Thus, hippocampal estradiol levels and sex modify chromatin states to enable long-lasting memory vulnerabilities to MACSs.
