Matching Items (22)

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Understanding the Impact of Phytoestrogens on Memory & the Cholinergic System

Description

Menopause is reproductive senescence characterized by a loss of ovarian estrogen and progesterone. Women can experience cognitive decline and other negative symptoms with the loss of ovarian hormones (Sherwin, 2006).

Menopause is reproductive senescence characterized by a loss of ovarian estrogen and progesterone. Women can experience cognitive decline and other negative symptoms with the loss of ovarian hormones (Sherwin, 2006). While hormone therapies (HT) can treat symptoms of menopause and may have neuroprotective properties, such as the potential to decrease the risk of Alzheimer's Disease (Behl & Manthey, 2000), there are many effects of current HTs that are not ideal. Indeed, optimizing conventional HTs has proven complex, indicating a need for alternative therapies. Phytoestrogens are estrogenic compounds found naturally in plants such as soybeans, that could provide new treatment options. Dietary phytoestrogens can benefit memory in the rodent model (Luine, 2006), although the mechanism underlying these effects is unclear. Basal forebrain cholinergic projections have been shown to mediate the cognitive benefits of estrogen (Gibbs, 2010); we hypothesize that phytoestrogens act similarly, via the cholinergic system, to impact memory. We administered varying doses of phytoestrogen-containing diets to ovariectomized female rats, and used the place recognition task to evaluate spatial memory. Brains were then analyzed for choline acetyltransferase (ChAT), the synthesizing enzyme for acetylcholine, in the vertical-diagonal bands (VDB) and the medial septum (MS) of the basal forebrain. Results showed that ChAT cell counts in the VDB were marginally higher with dietary phytoestrogen treatment. Further, VDB ChAT cell counts positively correlated with place recognition performance, indicating that animals with more VDB ChAT neurons exhibited better spatial memory performance. These results suggest that phytoestrogens might act similarly to natural, endogenously circulating estrogens, and identify phytoestrogens as a direction for investigation as a HT.

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Date Created
  • 2014-05

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Cognitive efficacy of three bioidentical, endogenously circulating estrogens given as hormone therapy: Extending prior findings and navigating into unchartered territory

Description

Women are now living longer than ever before, yet the age of spontaneous menopause has remained stable. This results in an increasing realization of the need for an effective treatment

Women are now living longer than ever before, yet the age of spontaneous menopause has remained stable. This results in an increasing realization of the need for an effective treatment of cognitive and physiological menopausal and post-menopausal symptoms. The most common estrogen component of hormone therapy, conjugated equine estrogens (CEE; Premarin) contains many estrogens that are not endogenous to the human body, and that may or may not be detrimental to cognition (Campbell and Whitehead, 1977; Engler-Chiurazzi et al., 2011; Acosta et al., 2010). We propose the use of a novel treatment option in the form of a naturally-circulating (bioidentical) estrogen called estriol. Due to estriol’s observed positive effects on synaptic functioning and neuroprotective effects in the hippocampus (Ziehn et al., 2012; Goodman et al., 1996), a brain structure important for spatial learning and memory, estriol is promising as a hormone therapy option that may attenuate menopausal- and age- related memory decline. In the current study, we administered one of the three bioidentical estrogens (17β-Estradiol, 4.0 µg/day; Estrone, 8.0 µg/day; Estriol, 8.0 µg/day) or the vehicle polyethylene glycol by subcutaneous osmotic pump to ovariectomized Fisher-344 rats. We compared these groups to each other using a battery of spatial learning tasks, including the water radial-arm maze (WRAM), Morris water maze (MM), and delayed-match-to-sample maze (DMS). We found that all estrogens impaired performance on the WRAM compared to vehicle, while 17β-estradiol administration improved overnight forgetting performance for the MM. The estriol group showed no cognitive enhancements relative to vehicle; however, there were several factors indicating that both our estriol and estradiol doses were too high, so future studies should investigate whether lower doses of estriol may be beneficial to cognition.

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Date Created
  • 2015-05

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Head Trauma in Professional Football Players: Implications for the Brain, the Game, and Society

Description

Sports related concussions, or mild traumatic brain injuries (mTBI), have recently increased in prevalence, and thus gained a great deal of recognition from the public and the media. While the

Sports related concussions, or mild traumatic brain injuries (mTBI), have recently increased in prevalence, and thus gained a great deal of recognition from the public and the media. While the acute symptoms associated with concussions are well known, which include headaches, dizziness, vomiting, and fatigue, recent research has indicated that there can be severe chronic consequences of multiple conditions. Most notably, a disease called Chronic Traumatic Encephalopathy (CTE) has been linked to multiple mTBIs, which produces symptoms similar to Alzheimer's disease and dementia, in addition to personality changes, increased suicidality, and in some cases death. This knowledge has led the NFL to take steps to protect their players, and increase both the understanding and awareness of the problems associated with multiple concussions. This comes with many problems, however, as players and fans alike are quick to resist any type of change to the rules or policies present in football, in fear that it may damage the integrity of the game. The NFL is thus forced into a difficult position, and must balance public opinion and player safety. There are things that can be done, however, that do not threaten the game itself, such as investing in concussion research and safety equipment design that will more effectively protect the brain from concussions.

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Date Created
  • 2013-05

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Cognitive Impact of Dietary Phytoestrogens

Description

There is preclinical evidence that the detrimental cognitive effects of hormone loss can be ameliorated by estrogen therapy (Bimonte, Acosta, & Talboom, 2010), however, one of the primary concerns with

There is preclinical evidence that the detrimental cognitive effects of hormone loss can be ameliorated by estrogen therapy (Bimonte, Acosta, & Talboom, 2010), however, one of the primary concerns with current hormone therapies is that they are nonselective, leading to increased risk of breast and endometrial cancers as well as heart disease. Thus, in order to achieve a successful and clinically relevant long-term hormone therapy option, it is optimal to find an estrogen therapy regimen that is selective to its target tissue. Recently, phytoestrogens have been found to exert selective, beneficial effects on cognition and brain. For example, genistein and diadzein produce neuroprotective effects in cognitive brain regions (Zhao, Chen, & Diaz Brinton, 2002). The purpose of this study was threefold: 1) to examine the cognitive impact of phytoestrogens in young ovariectomized rats, 2) to replicate the dose effects found in the Luine study (Luine et al., 2006), while controlling for manufacturer differences, and 3) to assess if the rodent diet used in our laboratory has an estrogenic-like cognitive impact.The current findings suggest that, at least for object memory, diets containing varying amounts of phytoestrogens can alter cognition, with diets containing high amounts of phytoestrogens showing potential benefits to this type of memory.

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Date Created
  • 2013-05

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Do anabolic steroids impact cognition? An evaluation of Androstenedione's impact on spatial cognitive performance in the young male rodent

Description

Following natural menopause, androstenedione becomes the main hormone secreted by the follicle-depleted ovaries. We have previously evaluated high physiological doses of androstenedione in the female rodent, and found relations between

Following natural menopause, androstenedione becomes the main hormone secreted by the follicle-depleted ovaries. We have previously evaluated high physiological doses of androstenedione in the female rodent, and found relations between higher androstenedione levels and spatial memory impairment; this relationship was shown when androstenedione levels were of endogenous, or exogenous, origin (Acosta et al., 2009, Camp et al., 2012). This androstenedione-induced memory impairment in females led us to question whether this androgen also impairs memory in males; no study has yet evaluated androstenedione's impact on cognition in the male rodent model. This is a clinically relevant question, as androstenedione is a steroid of abuse. In the current study, four-month old male rats were given either a daily injection of androstenedione, androstenedione with anastrozole or vehicle (polyethylene glycol). Subjects completed a battery of cognitive tasks evaluating spatial working, reference, and recent memory including the water radial arm maze (WRAM), Morris water maze (MM), and delayed match-to-sample maze (DMTS). We found that androstenedione administration impaired spatial cognitive performance in MM on early overnight forgetting and DMTS early recent memory trials across all days of testing. In addition, we found that androstenedione with anastrozole administration impaired spatial cognitive performance in the learning phases and early overnight forgetting in the MM but had no impact in DMTS testing. There were no significant differences in the WRAM maze for either group. Our findings suggest that androstenedione can impair spatial reference and early recent memory, and that anastrozole reverses this impairment for early recent memory, but not reference memory. Interpreted in the context of hormone conversion, androstenedione's effects on spatial learning and memory may be due, in part, to its conversion to estrone.

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Date Created
  • 2014-05

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The first in its class? The cognitive effects of the contraceptive hormone drospirenone when given with and without an estrogen

Description

Drospirenone (DRSP) is a novel, pharmacologically unique synthetic progestin with properties more similar to the endogenous progestogen, progesterone, than any other progestin currently on the market. While a significant amount

Drospirenone (DRSP) is a novel, pharmacologically unique synthetic progestin with properties more similar to the endogenous progestogen, progesterone, than any other progestin currently on the market. While a significant amount of research has been conducted on the risks associated with DRSP, the impact of DRSP on cognition, especially in reference to learning and memory, is not well understood. However, it is imperative to fully understand the cognitive effects of DRSP, both alone and in combination with EE (as taken in a combined oral contraceptive [COC]), so that women and their physicians can make a fully-informed decision when deciding to take a DRSP-containing COC. Study 1 examined the effects of three doses of DRSP in order to determine the optimal dose for combining with EE, and found that the medium dose of DRSP (30 µg/day) enhanced spatial working memory performance. In Study 2, the medium dose of DRSP from Study 1 was combined with low (0.125 µg/day) and high (0.3 µg/day) doses of EE to examine the effects of DRSP as taken with EE in a COC. The results from Study 2 indicated that when DRSP was combined with a low, but not high, dose of EE, spatial working memory impairments were seen at the highest working memory load. Anxiety-like behavior was evaluated using the OFT, and DRSP was shown to decrease measures of anxiety-like behavior. Additionally, while treatment with a high dose of EE decreased several measures of anxiety-like behavior, a low dose of EE did not, suggestive of a dose response. Taken together, the findings presented from both studies suggest that some of the cognitive effects of the combination of DRSP with EE are different than those of either hormone administered on its own. Further exploration in a preclinical, ovary-intact animal model is a next step to fully understand these effects in the translational context of a contraceptive, given that women taking an EE-DRSP combination are typically ovary-intact.

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Created

Date Created
  • 2017-05

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Dogs and Cognitive Dysfunction

Description

Alzheimer's disease affects a large number of Americans every year, and research on the causes and possible prevention continues to increase. Alzheimer's disease is a form of dementia that causes

Alzheimer's disease affects a large number of Americans every year, and research on the causes and possible prevention continues to increase. Alzheimer's disease is a form of dementia that causes problems with memory, thinking, and behavior and is thought to be caused by beta-amyloid plaques that form in the brain. In recent years, dogs have been used more and more as an animal model looking at Alzheimer's disease and cognitive dysfunction. Dogs serve as a reliable animal model because effected dogs naturally form the same beta-amyloid plaques that affected humans do as they age. Previous research has shown that older dogs perform worse on various memory tasks than do younger dogs, however researchers have struggled to find a test for dog cognitive dysfunction that is brief and can be performed in the home. The current study aimed to find a brief memory task that requires few materials, but is still reliable. The results of this study do not support the hypothesis that older dogs would perform worse than younger dogs if tested to find a treat with varying time delays of 15, 30, and 45 seconds. The results of this experiment showed a main effect of age (F = 8.40, d.f. 1, 19, p < 0.01) and delay (F = 15.14, d.f. 2, 30, p < 0.01), but age-delay interaction was not significant (F = 2.53, d.f. 2, 30, p = 0.09). Future studies should be performed using a larger sample size and this same protocol to attempt to raise the participation level of the dogs.

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Date Created
  • 2016-12

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Development of Brief Memory Tests for Use with Pet Dogs

Description

Brief memory tasks for use with pet dogs were developed using radial arm maze performance as a standard comparison measurement of memory capacity. Healthy pet dogs were first tested in

Brief memory tasks for use with pet dogs were developed using radial arm maze performance as a standard comparison measurement of memory capacity. Healthy pet dogs were first tested in a radial arm maze, where more errors made in completing the maze indicated poorer memory. These dogs were later tested with five novel memory tests, three of which utilized a treat placed behind a box with an identical distracter nearby. The treat placement was shown to each dog, and a 35 second delay, a 15 second delay with occluder, or a 15 second delay with room exit was observed before the dog could approach and find the treat. It was found that errors on the delayed match to sample (35 second delay) and occluder/object permanence (15 second delay with occluder) tasks were significantly positively correlated with the average number of errors made in the 8th trial of the radial arm maze (r =.58, p<.01** and r =.49, p<.05*, respectively) indicating that these new brief tests can reliably be used to assess memory in pet dogs.

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Date Created
  • 2015-05

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The effects of urbanization and human disturbance on problem solving in juvenile house finches (Haemorhous mexicanus)

Description

Urbanization exposes wildlife to many unfamiliar environmental conditions, including the presence of novel structures and food sources. Adapting to or thriving within such anthropogenic modifications may involve cognitive skills, whereby

Urbanization exposes wildlife to many unfamiliar environmental conditions, including the presence of novel structures and food sources. Adapting to or thriving within such anthropogenic modifications may involve cognitive skills, whereby animals come to solve novel problems while navigating, foraging, etc. The increased presence of humans in urban areas is an additional environmental challenge that may potentially impact cognitive performance in wildlife. To date, there has been little experimental investigation into how human disturbance affects problem solving in animals from urban and rural areas. Urban animals may show superior cognitive performance in the face of human disturbance, due to familiarity with benign human presence, or rural animals may show greater cognitive performance in response to the heightened stress of unfamiliar human presence. Here, I studied the relationship between human disturbance, urbanization, and the ability to solve a novel foraging problem in wild-caught juvenile house finches (Haemorhous mexicanus). This songbird is a successful urban dweller and native to the deserts of the southwestern United States. In captivity, finches captured from both urban and rural populations were presented with a novel foraging task (sliding a lid covering their typical food dish) and then exposed to regular periods of high or low human disturbance over several weeks before they were again presented with the task. I found that rural birds exposed to frequent human disturbance showed reduced task performance compared to human-disturbed urban finches. This result is consistent with the hypothesis that acclimation to human presence protects urban birds from reduced cognition, unlike rural birds. Some behaviors related to solving the problem (e.g. pecking at and eying the dish) also differed between urban and rural finches, possibly indicating that urban birds were less neophobic and more exploratory than rural ones. However, these results were unclear. Overall, these findings suggest that urbanization and acclimation to human presence can strongly predict avian response to novelty and cognitive challenges.

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Date Created
  • 2015-05

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Together but not for better? Conjugated equine estrogens, estradiol, androstenedione, and their interactions on spatial memory in C-57 mice

Description

Menopause is associated with a wide array of negative symptoms. As average lifespan increases due to advances in healthcare and technology, more women are spending a larger portion of their

Menopause is associated with a wide array of negative symptoms. As average lifespan increases due to advances in healthcare and technology, more women are spending a larger portion of their lives in a menopausal state low in estrogen and progesterone. Hormone therapies such as Conjugated Equine Estrogens (CEE) and the bioidentical estrogen, 17-estradiol (E2), are commonly prescribed to treat the negative symptoms of menopause. Our laboratory has previously shown that CEE has differential effects on cognitive ability depending on whether menopause is transitional (VCD) or surgical (ovariectomy, OVX). Further, the negative impact of CEE on cognitive function in a transitional ovary-intact model of menopause was associated with high levels of serum androstenedione; the primary hormone circulating in a follicle-deplete menopausal state. Here, we investigate the cognitive effects of these two common hormone therapies separately, and in conjunction with the hormone androstenedione, in a "blank-slate" OVX mouse model. We assessed cognitive ability using two behavioral tasks such at the Water Radial Arm Maze (WRAM, measuring spatial working and reference memory) and the Morris water maze (MM, measuring spatial reference memory). In the WRAM, every treatment group saw impaired performance compared to Vehicle but the combination group of E2 plus Androstenedione. In the MM, the combination group of E2 plus Androstenedione actually enhanced performance in the maze compared to every other comparable group. Translationally, these results suggest that CEE given in the presence of an androstenedione-dominant hormone milieu is impairing to cognition, E2 in this same manner is not. These results yield valuable insight into optimal hormone therapies for menopausal women.

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Created

Date Created
  • 2016-05