Memory In Ovariectomized Rats Research Articles

Therapeutic Effects Of Combined and Chronic Treatment of Tat-GluA23y and D-Serine on Cognitive Dysfunction in Postmenopausal Rats

ABSTRACT Background The incidence of Alzheimer’s disease (AD) in female gender compared with male has been addressed as a health concern, particularly in menopausal age. We here hypothesized that co-administration of NMDARs agonist (D-serine) and AMPARs endocytosis inhibitor (Tat-GluA23y) might be a potential target for alleviating memory impairment in sporadic Alzheimer model of rats. Methods Forty-eight female Wistar rats weighing 200–220 randomly divided into six groups. One month later, ovariectomized rats underwent stereotaxic surgery and were cannulated into the brain lateral ventricles. Streptozotocin was injected (3 mg/kg), then animals received the related treatments until the day 51, which experienced acquisition of spatial memory in Morris Water Maze test. Finally, the level of phosphorylated cAMP response element binding protein (CREB) in the hippocampus was measured by Western blotting. Results Co-administration of D-serine and GluA23y significantly enhanced the acquisition and retrieval of impaired spatial memory in ovariectomized rats with AD (p < .001). Compared to Glu-A 23, D-serine caused more improvement in the mentioned parameters above, however, these values for both groups were still significantly different from the control group (P < .05). Conclusion Simultaneous treatment with D-serine and GluA23y synergistically improved STZ induced spatial memory impairment in OVX rat, probably partly via increase in phosphorylated CREB protein.

High-intensity interval training improves long-term memory and increases hippocampal antioxidant activity and BDNF levels in ovariectomized Wistar rats

Menopause is the period in which women cease to produce the hormone estrogen, which can trigger physiological, cognitive, and behavioral changes. In this context, alternatives are needed that can reduce the effects provided by menopause, specifically in terms of cognitive and behavioral aspects. High-intensity interval training (HIIT) is an exercise protocol that has shown the potential to improve cognition by promoting an increase in antioxidant defenses and BDNF levels. Therefore, the aim of this study was to evaluate the effects of HIIT on behavior and hippocampal neurochemistry in ovariectomized adult rats. Four groups of rats were divided into: females without ovariectomy surgery and sedentary (SHAM-SED); females with ovariectomy surgery and sedentary (OVX-SED); females without ovariectomy surgery and trained (SHAM-HIIT); females with ovariectomy surgery and trained (OVX-HIIT). After the surgical procedure and the HIIT protocol, the animals underwent anxiety (elevated plus maze and open field) and memory (novel object recognition) tests. Corticosterone was measured in blood and BDNF levels and redox status were evaluated in the hippocampus. The OVX-SED group showed low BDNF levels and antioxidant enzymes, which may be linked to the observed memory impairments. The HIIT protocol (SHAM-HIIT and OVX-HIIT groups) increased the BDNF levels and antioxidant enzymes in the hippocampus, improving the animals' memory. However, HIIT also led to increased plasma corticosterone and anxiety-like behaviors. The ovariectomy procedure induced memory impairment probably due to reductions in hippocampal BDNF levels and redox imbalance. The HIIT protocol demonstrates promising results as an alternative to improve memory in ovariectomized rats.

Improvement of Cognitive Function in Ovariectomized Rats by Human Neural Stem Cells Overexpressing Choline Acetyltransferase via Secretion of NGF and BDNF.

Menopause is associated with memory deficits attributed to reduced serum estrogen levels. We evaluated whether an increase in brain-derived neurotrophic factor (BDNF) and nerve-growth factor (NGF) levels, through transplantation of choline acetyltransferase (ChAT)-overexpressing neural stem cells (F3.ChAT), improved learning and memory in ovariectomized rats. PD13 mouse neuronal primary culture cells were treated with estradiol or co-cultured with F3.ChAT cells; choline transporter1 (CHT1), ChAT, and vesicular acetylcholine transporter (VAChT) expression was evaluated using real-time PCR. The relationship between estrogen receptors (ERs) and neurotrophin family members was analyzed using immunohistochemistry. After the transplantation of F3.ChAT cells into OVx rats, we evaluated the memory, ACh level, and the expression of ER, neurotrophin family proteins, and cholinergic system. Estradiol upregulated CHT1, ChAT, and VAChT expression in ER; they were co-localized with BDNF, NGF, and TrkB. Co-culture with F3.ChAT upregulated CHT1, ChAT, and VAChT by activating the neurotrophin signalling pathway. Transplantation of F3.ChAT cells in OVX animals increased the ACh level in the CSF and improved memory deficit. In addition, it increased the expression of ERs, neurotrophin signaling, and the cholinergic system in the brains of OVX animals. Therefore, the estradiol deficiency induced memory loss by the down-regulation of the neurotrophin family and F3.ChAT could ameliorate the cognitive impairment owing to the loss or reduction of estradiol.

수영운동이 난소절제 쥐 혈중 지질, 해마의 BDNF mRNA, c-fos mRNA 발현 및 공간기억에 미치는 영향

The purpose of this study was to investigate the effects of swimming exercise on serum Lipid, BDNF mRNA and c-fos mRNA expression of hippocampus and spatial memory in ovariectomized rats. Sixteen week old female rat(S.D) were randomly divided into three groups(n=12 in each group): the normal control group(CON), control group with ovariectomized(OVA+Con) and swimming exercise group with ovariectomized(OVA+SE). The exercise program consisted of a swimming exercise administered for 12 weeks. After 12 weeks of swimming exercise training, uterus weight was significantly induced in swimming exercise group compared with ovariectomized control group. serum total cholesterol, trigryceride, LDL-C level were significantly reduced in swimming exercise group compared with ovariectomized control group. However, HDL-C levels was non significantly induced in swimming exercise group compared with ovariectomized control group. BDNF, c-fos mRNA expression of hippocampus were significantly induced in swimming exercise group compared with ovariectomized control group. Spatial memory was significantly induced in swimming exercise group compared with ovariectomized control group. It is concluded that there is a protective role for swimming exercise in reducing the risk of cardiovascular desease in ovariectomized rats.

Circulating Estradiol Regulates Brain-Derived Estradiol via Actions at GnRH Receptors to Impact Memory in Ovariectomized Rats.

Systemic estradiol treatment enhances hippocampus-dependent memory in ovariectomized rats. Although these enhancements are traditionally thought to be due to circulating estradiol, recent data suggest these changes are brought on by hippocampus-derived estradiol, the synthesis of which depends on gonadotropin-releasing hormone (GnRH) activity. The goal of the current work is to test the hypothesis that peripheral estradiol affects hippocampus-dependent memory through brain-derived estradiol regulated via hippocampal GnRH receptor activity. In the first experiment, intracerebroventricular infusion of letrozole, which prevents the synthesis of estradiol, blocked the ability of peripheral estradiol administration in ovariectomized rats to enhance hippocampus-dependent memory in a radial-maze task. In the second experiment, hippocampal infusion of antide, a long-lasting GnRH receptor antagonist, blocked the ability of peripheral estradiol administration in ovariectomized rats to enhance hippocampus-dependent memory. In the third experiment, hippocampal infusion of GnRH enhanced hippocampus-dependent memory, the effects of which were blocked by letrozole infusion. Results indicate that peripheral estradiol-induced enhancement of cognition is mediated by brain-derived estradiol via hippocampal GnRH receptor activity.

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

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 (10µg/day i.p. 17β-estradiol) groups for 3 (OVX+E3) and 21days 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 3weeks 17β-estradiol treatment may have an ameliorative effect on the memory through the central cholinergic system.

Rapid effects of the G-protein coupled oestrogen receptor (GPER) on learning and dorsal hippocampus dendritic spines in female mice

Recently, oestrogen receptors (ERs) have been implicated in rapid learning processes. We have previously shown that 17β-estradiol, ERα and ERβ agonists can improve learning within 40min of drug administration in mice. However, oestrogen action at the classical receptors may only in part explain these rapid learning effects. Chronic treatment of a G-protein coupled oestrogen receptor (GPER) agonist has been shown to affect learning and memory in ovariectomized rats, yet little is known about its rapid learning effects. Therefore we investigated whether the GPER agonist G-1 at 1μg/kg, 6μg/kg, 10μg/kg, and 30μg/kg could affect social recognition, object recognition, and object placement learning in ovariectomized CD1 mice within 40min of drug administration. We also examined rapid effects of G-1 on CA1 hippocampal dendritic spine density and length within 40min of drug administration, but in the absence of any learning tests. Results suggest a rapid enhancing effect of GPER activation on social recognition, object recognition and object placement learning. G-1 treatment also resulted in increased dendritic spine density in the stratum radiatum of the CA1 hippocampus. Hence GPER, along with the classical ERs, may mediate the rapid effects of oestrogen on learning and neuronal plasticity. To our knowledge, this is the first report of GPER effects occurring within a 40min time frame.

Activation of G-protein-coupled receptor 30 is sufficient to enhance spatial recognition memory in ovariectomized rats

In ovariectomized rats, administration of estradiol, or selective estrogen receptor agonists that activate either the α or β isoforms, have been shown to enhance spatial cognition on a variety of learning and memory tasks, including those that capitalize on the preference of rats to seek out novelty. Although the effects of the putative estrogen G-protein-coupled receptor 30 (GPR30) on hippocampus-based tasks have been reported using food-motivated tasks, the effects of activation of GPR30 receptors on tasks that depend on the preference of rats to seek out spatial novelty remain to be determined. Therefore, the aim of the current study was to determine if short-term treatment of ovariectomized rats with G-1, an agonist for GPR30, would mimic the effects on spatial recognition memory observed following short-term estradiol treatment. In Experiment 1, ovariectomized rats treated with a low dose (1μg) of estradiol 48h and 24h prior to the information trial of a Y-maze task exhibited a preference for the arm associated with the novel environment on the retention trial conducted 48h later. In Experiment 2, treatment of ovariectomized rats with G-1 (25μg) 48h and 24h prior to the information trial of a Y-maze task resulted in a greater preference for the arm associated with the novel environment on the retention trial. Collectively, the results indicated that short-term treatment of ovariectomized rats with a GPR30 agonist was sufficient to enhance spatial recognition memory, an effect that also occurred following short-term treatment with a low dose of estradiol.

Brain tissue oxidative damage as a possible mechanism for the deleterious effect of a chronic high dose of estradiol on learning and memory in ovariectomized rats

In addition to antioxidative effects, estrogens also exert pro-oxidative actions. The effect of chronic administration of a high dose of estradiol valerate on Morris water maze tasks and brain tissues oxidative damage was investigated. The Sham-Est and OVX-Est groups were treated with estradiol valerate (4 mg/kg) for 12 weeks. Escape latency and traveled path in the Sham-Est and OVX-Est groups were significantly higher than in the Sham and OVX groups (p<0.01 and p<0.001). In the probe trial, the animals of the Sham-Est and OVX-Est groups spent lower time in Q1 compared to Sham and OVX groups (p<0.05 and p<0.001). In Sham-Est and OVX-Est groups, the brain tissue total thiol concentration was significantly lower, and malondialdehyde (MDA) concentrations were higher than in the Sham and OVX groups (p<0.05 and p<0.001). It is concluded that administration of high exogenous levels of estradiol impairs performance and enhances oxidative stress.

Jujube promotes learning and memory in a rat model by increasing estrogen levels in the blood and nitric oxide and acetylcholine levels in the brain

The aim of this study was to observe the effects of jujube on learning and memory in ovariectomized rats. The effects of jujube on learning and memory in ovariectomized rats were observed using the Morris water maze method. The serum follicle-stimulating hormone (FSH), estrogen and luteinizing hormone (LH) levels, and the brain nitric oxide synthase (NOS) and acetylcholinesterase (AChE) levels of the rats were determined. The results indicated that jujube reduced the latency period and increased the number of crossings made by the ovariectomized rats in the Morris water maze test. Jujube also increased the serum estrogen level, reduced the serum FSH and corpus luteum LH levels, increased brain NOS activity and reduced AChE activity. The results indicate that jujube promoted the learning and memory of the ovariectomized rats. This effect may be correlated with the increase in the estrogen level in the blood, and the changes in the nitric oxide and acetylcholine levels in the brain.

Timing of multi-target therapy to effectively improve learning and memory in ovariectomized rats

Timing of multi-target therapy to effectively improve learning and memory in ovariectomized rats

Chronic treatment with the nitric oxide synthase inhibitor, L-NAME, attenuates estradiol-mediated improvement of learning and memory in ovariectomized rats

INTRODUCTION:The role of ovarian hormones and nitric oxide in learning and memory has been widely investigated.OBJECTIVE:The present study was carried out to evaluate the effect of the nitric oxide synthase (NOS) inhibitor, N (G)-nitro-L-arginine methyl ester (L-NAME), on the ability of estradiol to improve learning in OVX rats using the Morris water maze.METHODS:Forty rats were divided into five groups: (1) ovariectomized (OVX), (2) ovariectomized-estradiol (OVX-Est), (3) ovariectomized-L-NAME 10 (OVX-LN 10), (4) ovariectomized-L-NAME 50 (OVX-LN 50) and (5) ovariectomized-estradiol-L-NAME 50 (OVX-Est-LN 50). The animals in the OVX-Est group were treated with a weekly injection of estradiol valerate (2 mg/kg; i.m.). The OVX-LN 10 and OVX-LN 50 groups were treated with daily injections of 10 and 50 mg/kg L-NAME (i.p.), respectively. The animals in the OVX-Est-LN 50 group received a weekly injection of estradiol valerate and a daily injection of 50 mg/kg L-NAME. After 8 weeks, all animals were tested in the Morris water maze.RESULTS:The animals in the OVX-Est group had a significantly lower latency in the maze than the OVX group (p<0.001). There was no significant difference in latency between the OVX-LN 10 and OVX-LN 50 groups in comparison with the OVX group. The latency in the OVX-Est-LN 50 group was significantly higher than that in the OVX-Est group (p<0.001).CONCLUSION:These results show that L-NAME treatment attenuated estradiol-mediated enhancement of spatial learning and memory in OVX rats, but it had no significant effect in OVX rats without estrogen, suggesting an interaction of nitric oxide and estradiol in these specific brain functions.

Progesterone can enhance consolidation and/or performance in spatial, object and working memory tasks in Long–Evans rats

Progesterone has a ubiquitous role in reproduction and fitness and may influence cognitive performance. We examined the effects of administration of progesterone (a regimen that facilitates sexual behaviour) on consolidation of complex information in Long-Evans rats, Rattus norvegicus, that may be relevant for social engagement. We also examined the effects of subcutaneous progesterone administration (4 mg/kg versus oil vehicle placebo) on memory of ovariectomized rats during various cognitive tasks. Ovariectomized rats that received progesterone, versus the vehicle, immediately post-training were better able to find a hidden platform in the water maze. In a recognition task, rats that received progesterone spent more time in the novel arm of the Y-maze task than rats that received the vehicle. Ovariectomized rats that received progesterone immediately after training spent significantly more time exploring a novel object (compared to a familiar object) than did vehicle-administered rats. When socially relevant stimuli (i.e. objects with the scent of familiar or novel conspecifics) were used in the social cognition task, ovariectomized rats that received progesterone spent more time exploring the object with the novel conspecifics' scent than did vehicle-administered rats. Pairing of progesterone, but not the vehicle, conditioned a place preference to the originally nonpreferred side of the conditioning chamber. We found no significant differences in motor activity measures in these tasks due to progesterone treatment. These results suggest that progesterone's effects to improve cognitive processes with nonsocial and socially relevant stimuli, as well as have reinforcing effects, may underlie some of its salient effects on reproduction-related behaviours.

Effects of anthocyanins on learning and memory of ovariectomized rats

Estrogen deficit is associated with mental health disorders, emotional difficulties, memory impairment, and other cognitive failures. Recently, considerable attention has been paid to bioflavonoids and their properties as phytoestrogens to alleviate symptoms related to estrogen deficit. Anthocyanins are antioxidant flavonoids with various physiological activities. We have previously shown that anthocyanins inhibited depression-like symptoms in ovariectomized rats. The aim of the present study was to investigate the effects of anthocyanins on learning and memory of ovariectomized rats in a shuttle-box active avoidance test. Female Wistar rats (250-280 g) were housed in three groups: group 1, control, nonovariectomized rats; group 2, ovariectomized rats; and group 3, ovariectomized rats, treated with anthocyanins (200 mg/kg PO) for 15 days after ovariectomy. On the 25th day after ovariectomy, an active avoidance shuttle-box test was performed. In the shuttle-box test, ovariectomized rats showed significantly increased latency time and total errors and decreased number of avoidances in the learning sessions. The group of ovariectomized rats treated with anthocyanins had considerably increased number of avoidances and significantly decreased latency time and total errors during the learning sessions. In memory retention tests, significant differences were observed between control, ovariectomized rats and ovariectomized rats treated with anthocyanins. Our results suggest that anthocyanins improve learning and memory of rats with estrogen deficit caused by ovariectomy.

P.1.130 Interactions between estrogen, scopolamine and venlafaxine in their influence on spatial memory in ovariectomized rats

P.1.130 Interactions between estrogen, scopolamine and venlafaxine in their influence on spatial memory in ovariectomized rats

Estrogen improves response accuracy and attenuates the disruptive effects of Δ⁹-THC in ovariectomized rats responding under a multiple schedule of repeated acquisition and performance.

Despite evidence of an interaction between cannabinoids and estrogen in the brain, little information is available regarding the consequences of this interaction on behavior. A within-subjects design was used to examine the effects of estrogen and delta9-tetrahydrocannabinol (delta9-THC) on learning and memory in ovariectomized rats responding under a multiple schedule of repeated acquisition and performance. Treatment with low physiological levels of estrogen, delivered in Silastic capsules, improved response accuracy without affecting response rate during acquisition. Estrogen also attenuated the ability of delta9-THC (0.56- 3.2 mg/kg) to decrease response accuracy and rate during acquisition and response accuracy during performance. Results indicate that estrogen can improve accuracy during acquisition of a nonspatial operant task and can attenuate delta9-THC- induced behavioral deficits.

Posttraining Estradiol Injections Enhance Memory in Ovariectomized Rats: Cholinergic Blockade and Synergism

The present experiments examined acute posttraining estrogenic influences on memory in ovariectomized rats. In experiment 1 rats received a single 8-trial (30-s ITI) training session with a submerged escape platform located in the same quadrant of a circular water maze on all trials. Following trial 8, rats received a posttraining intraperitoneal injection of either an estradiol–cyclodextrin inclusion complex (0.1, 0.2, or 0.4 mg/kg) or saline. On a retention test session 24 h later, the escape latencies of rats given injections of estradiol (0.2 mg/kg) were significantly lower than those of saline-treated rats, indicating an enhancement of memory. Injections of estradiol delayed 2 h posttraining did not affect retention, demonstrating a time-dependent effect of estradiol on memory storage processes. In experiment 2a, posttraining injections of the cholinergic muscarinic receptor antagonist scopolamine (0.4 mg/kg) impaired memory in ovariectomized rats. In experiment 2b, the memory-enhancing effect of estradiol (0.2 mg/kg) was blocked by concurrent posttraining administration of a subeffective dose (0.1 mg/kg) of scopolamine, suggesting an interaction between estradiol and muscarinic cholinergic systems in memory modulation. In experiment 3a, posttraining injections of the cholinergic muscarinic receptor agonist oxotremorine (0.2 mg/kg) enhanced memory in ovariectomized rats. In experiment 3b, concurrent posttraining injection of a subeffective dose of estradiol (0.1 mg/kg) and a subeffective dose of oxotremorine (0.1 mg/kg) enhanced memory, indicating a synergistic effect of estradiol and muscarinic receptor activation on memory.