The Different Sensitivity of Dendritic Degeneration in Hippocampal and Cortical Neurons to Estrogen Decline in Female Aging Mice

Abstract

Aging is the most important risk factor for Alzheimer's disease (AD). Epidemiological studies reported that women have higher incidence of AD than men, which is associated with estrogen deficiency post menopause. The integrity of dendrites ensures normal neuronal function, and dendrite degeneration is one of the hallmarks in AD. However, the contribution of estrogen deficiency in dendritic remodeling during female aging is still unclarified. In the present study, female 18- and 22-month-old mice showed an age-dependent cognitive decline. Interestingly, female 18- and 22-month-old mice induced dendritic degeneration in both hippocampus and cortex, wherein the dendritic degeneration of hippocampal CA1 pyramidal neurons and cortical nonpyramidal neurons were more obvious in 18-month-old mice and that would not deteriorate in 22-month-old mice. The female mice after ovariectomy (OVX) 5 months induced similar changes in female 22-month-old mice indicating by cognitive decline and dendritic degeneration, however, dendritic degeneration of the hippocampal DG granular cells was less bad than that in female 22-month-old mice. Besides, estradiol (E2) level, and estrogen receptor α and β (ERα and ERβ) in hippocampus and cortex decreased in aged female and OVX mice. Importantly, E2 application rescued these changes induced by OVX. In conclusion, the female aging-induced dendritic remodeling existed regional differences, wherein hippocampal CA1 pyramidal neurons and cortical nonpyramidal neurons were the more vulnerable to onset of estrogen deficiency, while DG granular cells were more sensitive to age.