Effects of estrogen deprivation on memory and expression of related proteins in ovariectomized mice

Xue Tao; Mingzhu Yan; Lisha Wang; Yunfeng Zhou; Zhi Wang; Tianji Xia; Xinmin Liu; Ruile Pan; Qi Chang

doi:10.21037/atm.2020.02.57

Effects of estrogen deprivation on memory and expression of related proteins in ovariectomized mice

Ann Transl Med. 2020 Mar;8(6):356. doi: 10.21037/atm.2020.02.57.

Authors

Xue Tao¹, Mingzhu Yan¹, Lisha Wang¹, Yunfeng Zhou¹, Zhi Wang¹, Tianji Xia¹, Xinmin Liu^{1

2}, Ruile Pan¹, Qi Chang¹

Affiliations

¹ Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China.
² National Key Laboratory of Human Factors Engineering and the State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing 100094, China.

Abstract

Background: The ovariectomized (OVX) rodent model is most widely used for studying the influence of estrogen deprivation on memory. However, the results of these studies are inconsistent, in that the memory of OVX rodents shows either impairment or no change. These inconsistent outcomes increase the difficulty of researching neurochemical mechanisms and evaluating drug efficacy. One possible explanation for these discrepancies might be that the time point for memory examination after OVX varies considerably among studies. The aim of our study was to investigate the effects of estrogen deprivation on memory and the expression of memory-related proteins at different times after OVX.

Methods: Novel object recognition (NOR), step-through passive avoidance (STPA) and the Morris water maze (MWM) were performed to evaluate the memory performance of mice at different times after OVX. The expressions of BDNF, TrkB, ULK1 and LC3II/LC3I in the hippocampus were also assessed to explore the relevant mechanisms.

Results: After OVX, a significant memory impairment was found in the STPA test at 4 weeks. In the NOR and MWM tests, however, memory deficits were not observed until 8 weeks post-OVX. Interestingly, at 8 weeks, a memory rebound was found in the STPA test. In the hippocampus, the levels of BDNF and TrkB in OVX mice were markedly decreased at 4 and 8 weeks. Subsequently, a significant decrease in the ULK1 and LC3II/LC3I level in OVX mice was observed at 8 weeks.

Conclusions: Memory impairment in mice was observed as early as 4 weeks after OVX, although there was a possibility of memory rebound with the prolongation of estrogen deprivation. Eight weeks of estrogen deprivation would be more likely to induce hippocampus-dependent memory impairment. This progressive impairment of memory might be due to the downregulation of the BDNF/TrkB signaling pathway at the early post-OVX stage, while the decrease of autophagy level in the later stage might also contribute to these progressive alterations. The underlying relationship between the BDNF/TrkB signaling pathway and autophagy in this progressive impairment of memory requires further study.

Keywords: BDNF/TrkB signaling pathway; Ovariectomy (OVX); autophagy; estrogen deprivation; memory impairment.