Effects of estrogen and raloxifene on synaptic density in the hippocampal CA1 region of ovariectomized rats

Abstract

Introduction: The CA1 region of the hippocampus has an important role in learning and memory. It has been shown that estrogen deficiency may reduce the synaptic density in the region and that hormone replacement therapy may attenuate the reduction.

Objectives: This study aimed to evaluate the effects of estrogen and raloxifene on the synaptic density profile in the CA1 region of the hippocampus in ovariectomized rats.

Methods: Sixty ovariectomized three-month-old virgin rats were randomized into six groups (n = 10). Treatments started either three days (early treatment) or sixty days (late treatment) after ovariectomy. The groups received propylene glycol vehicle (0.5 mL/animal/day), equine conjugated estrogens (50 μg/animal/day), or raloxifene (3 mg/kg/day) either early or late after ovariectomy. The drugs were administered orally by gavage for 30 days. At the end of the treatments, the animals were anesthetized and transcardially perfused with ether and saline solution. The brains were removed and prepared for analysis under transmission electron microscopy and later fixed.

Results: Results showed a significant increase in the synaptic density profile of the hippocampal CA1 region in both the early estrogen (0.534 ± 0.026 µ/m²) and the early raloxifene (0.437 ± 0.012 µ/m²) treatment groups compared to the early or late vehicle-treated control groups (0.338 ± 0.038 µ/m² and 0.277 ± 0.015 µ/m² respectively).

Conclusions: The present data suggest that the raloxifene effect may be lower than that of estrogen, even early or late treatment, on synaptic density in the hippocampus.

Keywords: CA1 region; Estrogen; Hippocampus; Hormone therapy; Ovariectomy; Raloxifene.