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

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.

Osthole Ameliorates Estrogen Deficiency-Induced Cognitive Impairment in Female Mice

“…However, OVX females in our experiment did not exhibit recognition memory impairment after 4 weeks of OVX (it was 4 weeks after OVX when NORT was performed), as the sham and OST-treated groups did not outperform these OVX mice in the time spent exploring the novel object. Our results is in agreement with a previous report that 4 week OVX did not alter recognition memory (Tao et al, 2020) but not in agreement with another study in which 4 week OVX impaired recognition memory in the NORT in mice. Actually, there is a variation in the duration of OVX across studies reporting conflicting results (Fonseca et al, 2013;Mitra et al, 2016;Aggarwal et al, 2019;Tao et al, 2020), and this seems to be a contributing factor for these conflicting findings.…”

“…Our results is in agreement with a previous report that 4 week OVX did not alter recognition memory (Tao et al, 2020) but not in agreement with another study in which 4 week OVX impaired recognition memory in the NORT in mice. Actually, there is a variation in the duration of OVX across studies reporting conflicting results (Fonseca et al, 2013;Mitra et al, 2016;Aggarwal et al, 2019;Tao et al, 2020), and this seems to be a contributing factor for these conflicting findings. For example, impaired recognition memory in mice in the NORT was found after 1 week OVX (Mitra et al, 2016).…”

Emodin Promotes Autophagy and Prevents Apoptosis in Sepsis-Associated Encephalopathy through Activating BDNF/TrkB Signaling

“…On the other hand, Emodin is involved in autophagy and cognitive dysfunction during the neurons’ injury. For example, Emodin could inhibit aggregation of amyloid β peptide 1–42 and improve cognitive deficits in Alzheimer’s disease [14]. Moreover, Emodin could alleviate sepsis-induced injury via inducing autophagy [15, 16].…”

“…This result suggested that downregulation of BDNF/TrkB signaling may contribute to the neuronal injury. Moreover, inactivation of BDNF/TrkB signaling could result in promotion of cell apoptosis, inhibition of cell autophagy, and upregulation of inflammatory responses [9, 14, 17]. Based on these data, it can be supposed that BDNF/TrkB signaling might act as a key mediator in progression of SAE.…”

Sex‐dependent responsiveness of hippocampal neurons to sex neurosteroids: A role of Arc/Arg3.1

“…Finally, in numerous studies, it was shown that E 2 enhances memory consolidation 9 . The particular role of BDNF/TrkB with respect to E 2 ‐induced memory consolidation was also recently reported 65–68 …”