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

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.