The effects of carvacrol and p-cymene on Aß1-42 -induced long-term potentiation deficit in male rats.

AIMS: Alzheimer's disease (AD) is the most common type of dementia in which oxidative stress plays an important role. In this disease, learning and memory and the cellular mechanism associated with it, long-term potentiation (LTP), are impaired. Considering the beneficial effects of carvacrol (CAR) and p-cymene against AD, their effect was assessed on in vivo hippocampal LTP in the perforant pathway (PP)-dentate gyrus (DG) pathway in an Aß1-42 -induced rat model of AD. METHODS: Male Wistar rats were randomly assigned to five groups: sham: intracerebroventricular (ICV) injection of phosphate-buffered saline, Aß: ICV Aß1-42 injections, Aß + CAR (50 mg/kg), Aß + p-cymene (50 mg/kg), and Aß + CAR + p-cymene. Administration of CAR and p-cymene was done by gavage daily 4 weeks before and 4 weeks after the Aß injection. The population spike (PS) amplitude and field excitatory postsynaptic potentials (fEPSP) slope were determined in DG against the applied stimulation to the PP. RESULTS: Aß-treated rats exhibited impaired LTP induction in the PP-DG synapses, resulting in significant reduction in both fEPSP slope and PS amplitude compared to the sham animals. Aß-treated rats consumed either CAR or p-cymene separately (but not their combination), and showed an enhancement in fEPSP slope and PS amplitude of the DG granular cells. CONCLUSIONS: These data indicate that CAR or p-cymene can ameliorate Aß-associated changes in synaptic plasticity. Surprisingly, the combination of CAR and p-cymene did not yield the same effect, suggesting a potential interaction between the two substances.

The effect of hesperetin on estrogen receptor gene expression and its relationship with the downstream pathways of estrogen receptor alpha.

BACKGROUND: Estrogen receptor (ER) is a transcription factor that affects the expression of some genes involved in the progression and development of breast cancer (BC). Hesperetin (Hst) is a flavonoid that inhibits the proliferation of BC cells. In this study, we investigated the effect of Hst on the cell viability of MCF-7 cells and the gene expression of the ERα, ERß, IL-6, Ps2, and Cyclin D1. METHODS: In this study, cell viability was determined by MTT assay. The cells were seeded in RPMI-1640 medium and then exposed to different concentrations of Hst (0, 25, 50, 100, 200, and 400 µM) for 24 h, and IC50 was calculated. Real-time PCR was used to assess the expression of ERα, ERß, pS2, Cyclin D1, and IL-6 mRNA. MCF-7 cells were seeded in RPMI-1640 medium and then exposed to different concentrations of Hst (0, 25, 50, 100, and 200 µM) for 24 h. Real-time PCR was carried out using a Step One Real-Time PCR System (ABI, USA) and Amplicon SYBR Green reagents. RESULTS: The MTT assay revealed increased cytotoxicity with higher concentrations of Hst, and the IC50 was calculated at 200 µM. Real-time PCR analysis following treatment with Hst showed a significant increase in ERα gene expression at 25 µM of Hst and a decrease in expression at 50, 100, and 200 µM of Hst (p < 0.0001). ERß gene expression significantly decreased across all concentrations of Hst (p < 0.0001), while IL-6 gene expression decreased significantly in all concentrations (p < 0.0001). pS2 gene expression increased significantly with all concentrations of Hst (p < 0.0001), while Cyclin D1 gene expression did not significantly decrease upon Hst exposure (p > 0.05). CONCLUSIONS: The results of our study demonstrate that Hst has the ability to induce cell death in MCF-7 cells. Furthermore, it was observed that Hst reduces the expression of the ER gene and enhances its activity, which can affect the downstream pathways of the ER.

The role of men's forgiveness in marital satisfaction and coping strategies of infertile iranian women.

BACKGROUND: Infertility and its related problems create tensions in infertile women, which may lead to reduced marital satisfaction and the use of ineffective coping strategies. Considering the important role of forgiveness, marital satisfaction and effective coping strategies in the quality of life of infertile couples, and taking into account the growing number of Iranian infertile couples, this study was conducted to determine the relationship between men's forgiveness, marital satisfaction, and coping strategies of infertile Iranian women. METHODS: This cross-sectional study included 200 Iranian infertile couples. The research environment was the most equipped infertility center in the west of Iran. Sampling was continuous. Data collection tools used included a self-generated demographic and fertility questionnaire, the Family Forgiveness Scale (FFS), the Index of Marital Satisfaction (IMS), and the Ways of Coping Questionnaire-revised (WOCQ-R). RESULTS: Husbands' forgiveness had a significant direct relationship with the marital satisfaction of infertile women (r = -0.27, p < 0.001). However, there was no significant correlation between Husbands' forgiveness, emotion-focused, and problem-focused coping of infertile women. Among the subscales of forgiveness, only the subscale of recognition had inversely correlated with the emotional coping of infertile women. CONCLUSION: The results showed that the higher the forgiveness of husbands, the higher the marital satisfaction of infertile women. Also, with the increase of husbands' forgiveness in the recognition subscale, the use of emotion-focused coping decreased in infertile women. Based on the results with empowering the husbands of infertile women with forgiveness skills, it is possible to take a step towards marital satisfaction and thus improve the quality of life of infertile women.

Effectiveness of coenzyme Q10 on learning and memory and synaptic plasticity impairment in an aged Aß-induced rat model of Alzheimer's disease: a behavioral, biochemical, and electrophysiological study.

RATIONALE: Aging is the major risk factor for Alzheimer's disease (AD), and cognitive and memory impairments are common among the elderly. Interestingly, coenzyme Q10 (Q10) levels decline in the brain of aging animals. Q10 is a substantial antioxidant substance, which has an important role in the mitochondria. OBJECTIVE: We assessed the possible effects of Q10 on learning and memory and synaptic plasticity in aged ß-amyloid (Aß)-induced AD rats. METHODS: In this study, 40 Wistar rats (24-36 months old; 360-450 g) were randomly assigned to four groups (n = 10 rats/group)-group I: control, group II: Aß, group III: Q10; 50 mg/kg, and group IV: Q10+Aß. Q10 was administered orally by gavage daily for 4 weeks before the Aß injection. The cognitive function and learning and memory of the rats were measured by the novel object recognition (NOR), Morris water maze (MWM), and passive avoidance learning (PAL) tests. Finally, malondialdehyde (MDA), total antioxidant capacity (TAC), total thiol group (TTG), and total oxidant status (TOS) were measured. RESULTS: Q10 improved the Aß-related decrease in the discrimination index in the NOR test, spatial learning and memory in the MWM test, passive avoidance learning and memory in the PAL test, and long-term potentiation (LTP) impairment in the hippocampal PP-DG pathway in aged rats. In addition, Aß injection significantly increased serum MDA and TOS levels. Q10, however, significantly reversed these parameters and also increased TAC and TTG levels in the Aß+Q10 group. CONCLUSIONS: Our experimental findings suggest that Q10 supplementation can suppress the progression of neurodegeneration that otherwise impairs learning and memory and reduces synaptic plasticity in our experimental animals. Therefore, similar supplemental Q10 treatment given to humans with AD could possibly provide them a better quality of life.

Policosanol protects against Alzheimer's disease-associated spatial cognitive decline in male rats: possible involved mechanisms.

RATIONALE: Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by cognitive decline and synaptic failure. OBJECTIVE: The present study was designed to explore the possible protective effects of policosanol (PCO) on spatial cognitive capacity, long-term potentiation (LTP) induction, oxidant/antioxidant status, and Aß plaques formation in an AD rat model induced by intracerebroventricular (ICV) injection of Aß1-40. METHODS: Healthy adult male Wistar rats were randomly divided into control, sham (ICV injection of 5 µl phosphate-buffered saline), AG (50 mg/kg; P.O., as PCO vehicle), PCO (50 mg/kg; P.O.), AD model (ICV injection of 5 µl Aß), AD + AG (50 mg/kg; P.O.), and AD + PCO (50 mg/kg; P.O.). Treatments were performed for eight consecutive weeks. At the end of the treatment course, spatial learning and memory functions, hippocampal long-term potentiation (LTP) induction, malondialdehyde (MDA), and total thiol group (TTG) levels, as well as the formation of Aß plaques, were examined. RESULTS: The results showed that injection of Aß reduced spatial learning and memory abilities in the Barnes maze test, which was accompanied by decreases in field excitatory postsynaptic potential (fEPSP) slope, population spike (PS) amplitude, and TTG level and increases in Aß plaque accumulation and MDA content. In contrast, PCO treatment improved all the above-mentioned changes in the Aß-infused rats. CONCLUSIONS: The results suggest that amelioration of hippocampal synaptic plasticity impairment, modulation of oxidant/antioxidant status, and inhibition of Aß plaque formation by PCO may be the mechanisms behind its protective effect against AD-associated spatial cognitive decline.

The Protective Effects of Policosanol on Learning and Memory Impairments in a Male Rat Model of Alzheimer's Disease.

Alzheimer's disease (AD), the most common form of dementia, is characterized by a progressive decline in cognitive performance and memory formation. The present study was designed to investigate the effect of policosanol (PCO) on cognitive function, oxidative-antioxidative status, and amyloid-beta (Aß) plaque formation in an AD rat model induced by intracerebroventricular (ICV) injection of Aß1-40. Healthy adult male Wistar rats were randomly divided into seven groups: control, sham (5 µL, ICV injection of phosphate-buffered saline), AD model (5 µL, ICV injection of Aß), acacia gum (50 mg/kg, 8 weeks, gavage), PCO (50 mg/kg, 8 weeks, gavage), AD + acacia gum (50 mg/kg, 8 weeks, gavage), and AD + PCO (50 mg/kg, 8 weeks, gavage). During the ninth and tenth weeks of the study, the cognitive function of the rats was assessed by commonly used behavioral paradigms. Subsequently, oxidative-antioxidative status was examined in the serum. Moreover, compact Aß plaques were detected by Congo red staining. The results showed that injection of Aß impaired recognition memory in the novel object recognition test, reduced the spatial cognitive ability in the Morris water maze, and alleviated retention and recall capability in the passive avoidance task. Additionally, injection of Aß resulted in increased total oxidant status, decreased total antioxidant capacity, and enhanced Aß plaque formation in the rats. Intriguingly, PCO treatment improved all the above-mentioned neuropathological changes in the Aß-induced AD rats. The results suggest that PCO improves Aß-induced cognitive decline, possibly through modulation of oxidative-antioxidative status and inhibition of Aß plaque formation.

Impairment in social interaction and hippocampal long-term potentiation at perforant pathway-dentate gyrus synapses in a prenatal valproic acid-induced rat model of autism.

It is well established that prenatal valproic acid exposure in rats leads to autism-like behaviours and social deficits. Long-term potentiation changes in the brain have been proposed as a potential mechanism in the development of autistic behaviour. However, there are controversies regarding the effect of in utero valproic acid exposure on long-term potentiation. This study examined the social interaction and long-term potentiation induction in perforant pathway-dentate gyrus synapses in male offspring of a rat model of autism induced by prenatal exposure to valproic acid. On Embryonic Day 12.5, the pregnant dams received an injection of 500 mg/kg valproic acid (intraperitoneal) to produce the autism model. The sociability test was performed between Postnatal Days 37 and 40. The offsprings were urethane-anaesthetized and placed into a stereotaxic apparatus for surgery, electrode implantation and field potential recording on Postnatal Days 45-55. In the dentate gyrus region, excitatory postsynaptic potential slope and population spike amplitude were measured. Valproic acid-exposed offspring showed significantly impaired social interaction. The birth weight in valproic acid-exposed rats was significantly lower than in control rats. The ability of dentate gyrus synapses to induce long-term potentiation was hampered by valproic acid exposure. The decreasing excitatory postsynaptic potential slope and population spike amplitude of long-term potentiation provide evidence in favour of this notion. It is widely supposed that the hippocampus plays a central role in the process of learning and memory as well as social interaction and social memory. Therefore, deficiencies in hippocampal synaptic plasticity may be responsible, at least in part, for the social interaction deficits in valproic acid-exposed rats.

Sex differences in spatial learning and memory and hippocampal long-term potentiation at perforant pathway-dentate gyrus (PP-DG) synapses in Wistar rats.

BACKGROUND: Recent studies show that gender may have a significant impact on brain functions. However, the reports of sex effects on spatial ability and synaptic plasticity in rodents are divergent and controversial. Here spatial learning and memory was measured in male and female rats by using Morris water maze (MWM) task. Moreover, to assess sex difference in hippocampal synaptic plasticity we examined hippocampal long-term potentiation (LTP) at perforant pathway-dentate gyrus (PP-DG) synapses. RESULTS: In MWM task, male rats outperformed female rats, as they had significantly shorter swim distance and escape latency to find the hidden platform during training days. During spatial reference memory test, female rats spent less time and traveled less distance in the target zone. Male rats also had larger LTP at PP-DG synapses, which was evident in the high magnitude of population spike (PS) potentiation and the field excitatory post synaptic potentials (fEPSP) slope. CONCLUSIONS: Taken together, our results suggest that sex differences in the LTP at PP-DG synapses, possibly contribute to the observed sex difference in spatial learning and memory.

Effects of vanillic acid on Aß1-40-induced oxidative stress and learning and memory deficit in male rats.

Alzheimer's disease (AD) is a neurodegenerative disease, in which the accumulation of ß-amyloid (Aß) peptide in the extracellular space causes a progressive reduction in cognitive performance. Aß stimulates active oxygen species generation leading to oxidative stress and neural cell death. Vanillic Acid (VA) is the oxidant form of vanillin widely found in vanilla beans. VA has many properties, such as suppressing apoptosis and eliminating the harmful effects of oxidative stress in animal models. The VA effects on impaired learning and memory in Aß rats were assessed. Forty adults male Wistar rats were assigned to the following five groups in random: the control, sham (received saline (vehicle) via intracerebroventricular (ICV) injection), Aß (received Aß1-40 via ICV injection), VA (50 mg/kg by oral gavage once a day through four weeks), and Aß + VA (50 mg/kg) groups. Open field test, novel object recognition (NOR) test, Morris water maze (MWM) test, and passive avoidance learning (PAL) task were performed, and finally, we determined the malondialdehyde (MDA), total antioxidant capacity (TAC) and total oxidant status (TOS) levels. Aß decreased the cognitive memory in NOR, spatial memory in MWM, and passive avoidance memory in PAL tests. In contrast, VA improved learning and memory in the treated group. Aß significantly increased MDA and TOS and decreased TAC levels, whereas VA treatment significantly reversed TAC, TOS and MDA levels. In conclusion, VA decreased the Aß effects on learning and memory by suppressing oxidative stress and can be regarded as a neuroprotective substance in AD.

Vanillic acid attenuates amyloid ß1-40-induced long-term potentiation deficit in male rats: an in vivo investigation.

Objectives: Alzheimer disease (AD) is a neurodegenerative disorderliness that involves deductible progressive cognition function caused by amyloid-beta (Aß) peptide accumulation in the interstitial space. The increase of Aß stimulates all kinds of active oxygen and causes oxidative stress and apoptosis. In this investigation, we researched the neuroprotective impacts of vanillic acid (VA) on the Aß-induced (Aß1-40) long-term potentiation (LTP) of the hippocampus - a commonly probed synaptic plasticity model that happens at the same time as memory and learning - in the AD rats.Methods: Forty-five male Wistar rats were categorized into five groups (n = 8 rats/group, 200-220 g), and studied as control (standard diet), sham (vehicle), VA (50 mg/kg), Aß and Aß + VA (50 mg/kg) groups. In vivo electrophysiological recordings were implemented after the stereotaxic surgery to gauge the excitatory postsynaptic potential (EPSP) slope and population spike (PS) amplitude in the dentate gyrus of the hippocampus. By the stimulation at high-frequency of the perforate pathway, long-term potentiation (LTP) was induced. To assess the plasma levels of malondialdehyde (MDA) and total thiol group (TTG), blood samples were garnered.Results: In the Aß-injected rats, EPSP slope, and PS amplitude were significantly reduced after the induction of LTP. Thus, the findings demonstrate that VA decreases the impacts of Aß on LTP; also, the treatments through VA neuroprotective against the negative effects of Aß on the synaptic plasticity of the hippocampus can decrease the MDA levels and also increase the TTG levels significantly.Discussion: Therefore, based on this experiment on male rats, VA has neuroprotective effects and antioxidants benefits against the Aß-mediated inhibition of long-term potentiation.