Abstract
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.
Highlights
With the increasing of elderly population in the world, more and more individuals are suffering from senile dementia
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)
Www.impactjournals.com/oncotarget and 18 M + E2 groups, we found marked swelling of mitochondria coupled with disappeared cristae in 18 M group (Figure 2E1), which could be prevented by E2 administration (Figure 2F1)
Summary
With the increasing of elderly population in the world, more and more individuals are suffering from senile dementia. Instead of benefiting the cerebral functions, HRT was found detrimental to women aged 65 or older [5, 6], while no apparent negative effect was found in women aged from 50 to 59 [8] This disparity of therapeutic effects may due to the difficulty for HRT to diminish the established pathological changes in patients more than 65 years old [9, 10, 11]. Overall, these phenomena suggest that initiating estrogen therapy at the early years of postmenopause (before ages 50 to 60 years) would in all probability be better than that at the late stage of postmenopause (at ages of more than 65 to 79 years). Exploring the pathophysiological alterations of brain at the early stage of postmenopause and identifying the effects www.impactjournals.com/oncotarget of estrogen (E2) in this process will greatly improve our understandings of HRT for the prevention of cognitive impairment in women
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
