Estrogen deficiency is associated with hippocampal morphological remodeling of early postmenopausal mice

Estrogen (E2) deficiency is reported to involve in the impairment of cognition in postmenopausal women. However, the morphological basis is still unclear. In the present study, using transmission electron microscopy (TEM), we observed the ultrastructure of hippocampus in female C57BL/6 mice at the age of 18 months (18 M) which is considered as the early stage of postmenopause (n = 8). Compared with control mice aged 6 M (n = 8), we identified that the morphological changes in the hippocampus of these menopausal mice were mitochondrial damage, lipofuscin deposition and microtubule degradation. Notably, after E2 was subcutaneously injected into mice aged 16 M with a dosage of 3.5 μg/kg every three days for two months in the 18 M + E2 group (n = 8), mitochondrial damage and lipofuscin deposition in the DG region of hippocampus were prevented, but the degraded microtubules in the hippocampus of postmenopausal mice were failed to restore. These data suggest that hippocampal ultrastructure remodeling in mice can be initiated at the early stage of postmenopause, E2 supplementation could only have an effect on mitochondrial damage and lipofuscin increase.