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Rationale <p>Impaired fear memory extinction is a core symptom of post-traumatic stress disorder (PTSD). Alleviating pathological fear memory is crucial for treating PTSD and related fear disorders.</p> Objectives <p>17β-estradiol (17β-E2) critically regulates hippocampal learning and memory. This study explored effects of gonadal and hippocampal 17β-E2 on cognitive function during fear memory reconsolidation in a rat PTSD model.</p> Methods <p>In female rats, ovariectomy with intraperitoneal 17β-E2 injection manipulated gonadal hormone levels, while intracerebral letrozole regulated hippocampal 17β-E2 synthesis.</p> Results <p>SPS-CFC model rats showed enhanced fear responses and anxiety-depression-like behaviors during fear memory reconsolidation. Elevated 17β-E2 ameliorated these PTSD-like phenotypes. Hippocampal mRNA and protein levels of PSD‑95, ERK1/2, p‑ERK1/2, and BDNF were upregulated, and synaptic structure improved.</p> Conclusions <p>These findings demonstrate that both gonadal-derived and hippocampus-derived 17β-E2 relieve cognitive deficits and emotional disorders during fear memory reconsolidation in PTSD model rats, providing a potential target for PTSD intervention.</p>

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17β-Estradiol alleviates cognitive deficits by modulating fear memory reconsolidation in a PTSD rat model

  • 期刊论文

  • 发表日期：

    2026年4月25日

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  • Han Wang,
  • Han Lin,
  • Zilong Zhong,
  • Baoying Jiang,
  • Siyi Li,
  • Jiahao Tang,
  • Xiaoping Zhou,
  • Guohui Zhu,
  • Yang Liu,
  • Wenhao Han,
  • Jinhua Dou,
  • Lin Sun

摘要

Rationale

Impaired fear memory extinction is a core symptom of post-traumatic stress disorder (PTSD). Alleviating pathological fear memory is crucial for treating PTSD and related fear disorders.

Objectives

17β-estradiol (17β-E2) critically regulates hippocampal learning and memory. This study explored effects of gonadal and hippocampal 17β-E2 on cognitive function during fear memory reconsolidation in a rat PTSD model.

Methods

In female rats, ovariectomy with intraperitoneal 17β-E2 injection manipulated gonadal hormone levels, while intracerebral letrozole regulated hippocampal 17β-E2 synthesis.

Results

SPS-CFC model rats showed enhanced fear responses and anxiety-depression-like behaviors during fear memory reconsolidation. Elevated 17β-E2 ameliorated these PTSD-like phenotypes. Hippocampal mRNA and protein levels of PSD‑95, ERK1/2, p‑ERK1/2, and BDNF were upregulated, and synaptic structure improved.

Conclusions

These findings demonstrate that both gonadal-derived and hippocampus-derived 17β-E2 relieve cognitive deficits and emotional disorders during fear memory reconsolidation in PTSD model rats, providing a potential target for PTSD intervention.