| First Author | Hokenson RE | Year | 2026 |
| Journal | Neuron | Volume | 114 |
| Issue | 8 | Pages | 1454-1472.e8 |
| PubMed ID | 41638202 | Mgi Jnum | J:389385 |
| Mgi Id | MGI:8323126 | Doi | 10.1016/j.neuron.2025.12.037 |
| Citation | Hokenson RE, et al. (2026) Hippocampal estrogen levels, receptor types, and epigenetics contribute to sex-specific memory vulnerabilities to concurrent acute stresses. Neuron 114(8):1454-1472.e8 |
| abstractText | 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 17beta-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)beta activation in resilient estrus females increased chromatin permissiveness and enduring vulnerability to MACSs, while ERalpha 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. |
