Introduction : The aim of this preliminary study was to evaluate the effect of long-term progesterone (P4) treatment on structural and functional deficits associated with the hippocampus. Material and methods : Mice served as sham controls or were bilaterally ovariectomized (Ovx), and a 90-day regimen of placebo or P4 was applied to the animal. After the administration, the acquisition and retrieval of mice in contextual fear conditioning (CFC) and a water maze were examined. Hippocampal tissues from some mice in each group were stained with cresyl violet, and the remainder were taken for determining the antioxidant power. Results : Compared with placebo controls, the time spent on freezing was higher and the latencies were longer for mice given high-dose P4 (HP) (p < 0.05) in CFC, and the HP group also had longer searching time spent in the target quadrant (p < 0.05) in the water maze. Compared with placebo controls, the cell number of hippocampus CA1, CA3 and DG was significantly higher in the HP group (p < 0.05), and the thickness of the cell layer in CA1 and DG was also higher in the HP group (p < 0.05). All the oxidative stress biomarkers show that the antioxidative activity in hippocampus tissue from the HP and LP groups is higher than that in placebo controls (p < 0.05). Conclusions : Ovx impairs learning and memory of mice, which can be rescued by a long-term regimen of HP via its antioxidant effects.
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