Estrogen deficiency exacerbates learning and memory deficits associated with glucose metabolism disorder in APP/PS1 double transgenic female mice

Alterations in glucose metabolism occur in the brain in the early stage of Alzheimer's disease(AD),and menopausal women have more severe metabolic dysfunction and are more prone to dementia than men.Although estrogen deficiency-induced changes in glucose metabolism have been previously studied in animal models,their molecular mechanisms in AD remain elusive.To investigate this issue,double transgenic(APP/PS1)female mice were subjected to bilateral ovariectomy at 3 months of age and were sacrificed 1 week,1 month and 3 months after surgery to simulate early,middle and late postmenopause,respectively.Our analysis demonstrated that estrogen deficiency exacerbates learning and memory deficits in this mouse model of postmenopause.Estrogen deficiency impairs the function of mitochondria in glucose metabolism.It is possible that the occurrence of AD is associated with the aberrant mitochondrial ERβ-mediated IGF-1/IGF-1R/GSK-3βsignaling pathway.In this study,we established a potential mechanism for the increased risk of AD in postmenopausal women and proposed a therapeutic target for AD due to postmenopause.

Computational Model for the Underlying Mechanisms Regulating Bone Loss by Mechanical Unloading and Estrogen Deficiency

The objective of this paper is to investigate the different effects of disuse and estrogen deficiency on bone loss and the underlying mechanisms.A mechanical-biological factors coupled computational model was built to simulate different patterns of bone loss induced in female rats by hind limb unloading,ovariectomy,or both in an animal study.A remodeling analysis was performed on a representative cross section of 6 mm2 of cancellous bone in the distal femoral metaphysis of the rats.The BMU activation frequency,the refilling rate,and the principal compressive strain in the state of mechanical unloading and estrogen deficiency were simulated to interpret the underlying mechanisms.Simulated bone loss patterns due to mechanical unloading,estrogen deficiency,or both all corresponded with the experimental observations.The results show that mechanical unloading and estrogen deficiency cause different bone loss patterns;moreover,mechanical unloading induces a greater degree of bone loss than estrogen deficiency,which can lead to improved treatment and prevention strategies for osteoporosis.