Chronic (3-Weeks) Treatment of Estrogen (17β-Estradiol) Enhances Working and Reference Memory in Ovariectomized Rats: Role of Acetylcholine

Abstract

Recently there has been a growing interest in the effects of estrogen on cognitive functions. In this study, we aimed to examine 17β-estradiol treatment on working and reference memory in ovariectomized rats. We also examined the changes in the acetylcholine (ACh) levels in the brain areas associated with learning and memory. The study was performed on Sprague-Dawley type 3-month-old female rats. The rats were divided into four groups as control, ovariectomy (OVX), and OVX and estrogen treatment (10 µg/day i.p. 17β-estradiol) groups for 3 (OVX + E3) and 21 days OVX + E21). The rats were trained on eight arm radial maze task with eight arms baited to assess spatial memory, in addition four arms baited to assess both working and reference memory performances. The electron microscope images of the ACh vesicles in the frontal cortex, temporal cortex and hippocampus areas of the brain which are important regions for learning and memory were screened. Results showed that long term 17β-estradiol treatment has positive effects on both reference memory and working memory and that ACh vesicles increased in the examined brain areas, especially in hippocampus. Our results suggest that 3 weeks 17β-estradiol treatment may have an ameliorative effect on the memory through the central cholinergic system.

Estrogen deficiency induces memory loss via altered hippocampal HB-EGF and autophagy

“…Estrogen prevents aberrant hippocampal neuronal apoptosis and cognitive deficits (Sales et al 2010, Uzum et al 2016, Yazgan & Naziroglu 2017, and the present study establishes the contribution of a controlled autophagy mechanism in estrogen-mediated neuroprotection. Here, we essentially demonstrated that estrogen deficiency up-regulates the expression of autophagy proteins such as Beclin1, LC3 and ATG7 along with the levels of ATG5/ATG12 conjugate within the hippocampus, indicative of an estrogen-regulated phagophore elongation and association with the autophagic vesicles.…”

“…Correspondingly, ovarian failure and estrogen deficiency, which characterize menopause in women, suppress cerebral ER levels (Qu et al 2013, Fang et al 2018 and alter neuronal functions, including cognition (Kim et al 2016, Djiogue et al 2018. Estrogen deficiency induces hippocampal apoptosis, neuronal loss (Sales et al 2010, Yazgan & Naziroglu 2017 and cognitive dysfunctions (Kim et al 2016, Djiogue et al 2018, while estradiol therapy reduces apoptosis and improves learning-memory performances (Sales et al 2010, Uzum et al 2016, Yazgan & Naziroglu 2017. However, the underlying mechanisms remain obscure.…”

Effects of neonatal 17α-ethinyloestradiol exposure on female-paced mating behaviour in the rat

“…In contrast, it has been revealed that oestrogens have critical beneficial effects in addition to reproduction. For instance, adult female rats which received 10 μg day −1 17β‐oestradiol for 3 weeks demonstrated enhanced working and reference memory (Uzum et al, ). Another study suggests oestrogens could attenuate disease‐associated cognitive deficits and reduce Alzheimer's disease risk (Engler‐Chiurazzi et al, ).…”

The Role of Estrogen in Anxiety-Like Behavior and Memory of Middle-Aged Female Rats

“…A large number of studies have shown that ovariectomy may induce cognitive dysfunction in young (13)(14)(15)(16) and also in middle-aged rats (29,30,43), while estrogens may improve learning and memory performance following ovariectomy in both, young (15,24,(59)(60)(61) and middle-aged females (21-23, 25, 29, 31). However, OVX females in our experiment exhibited mild memory impairment only, and the estradioltreated group did not outperform vehicle-treated OVX rats.…”