Biomedical subjects

Donna L Korol

Publications and source records attributed to Donna L Korol.

10 recordsLinked to original sources

PubMed2006

Estrogen modulates place learning through estrogen receptors in the hippocampus.

Moderate elevations in circulating estradiol enhance learning in tasks that tap place learning strategies such as those requiring the use of extramaze cues. Use of place learning strategies is particularly impaired by damage to the hippocampus, a structure shown to be sensitive to estrogen treatments. We have shown that direct estrogen infusions into the dorsal hippocampus, and not the dorsolateral striatum, enhance place learning, suggesting that the hippocampus may be an important modulatory site for the effects of estrogen on place learning. The current experiment tested whether the hippocampus is indeed a critical site of estrogen modulation through classical estrogen receptors. Young adult female Sprague-Dawley rats were ovariectomized for 21 days and given systemic injections (0.1 ml) of sesame oil (OIL) or 10 microg of 17beta-estradiol-benzoate (E2), 48 and 24 h before being trained on a place task. Twenty-four hours prior to the first systemic injection, separate groups of rats received bilateral hippocampal implants of either the antiestrogen ICI 182,780 (ICI) or cholesterol vehicle. Implants were maintained until and throughout training. Intrahippocampal ICI reversed the enhancement in place learning seen with systemic E2 treatment. Unexpectedly, intrahippocampal ICI in OIL-treated rats also enhanced place learning. These data suggest that ICI may have some mixed agonist and antagonist effects in the hippocampus and that estrogen enhances place learning through activation of estrogen receptors located in the hippocampus.

Animals↗

PubMed2006

Interactive effects of fitness and hormone treatment on brain health in postmenopausal women.

Recent research in rodents suggests that extended and chronic hormone therapy can exacerbate memory impairments and irreversibly damage cells. However, aerobic fitness regimens have been shown to spare brain tissue and cognitive function. In addition, interactions between estrogen treatment and exercise have been reported in rodents. However, whether aerobic fitness and hormone treatments show interactive effects on human brain tissue and cognition has yet to be determined. Here we report two unique and important results: (a) HRT treatment up to 10 years in duration spares gray matter in prefrontal cortex and is associated with better performance on measures of executive function, whereas HRT treatment beyond 10 years in duration increases the degree of prefrontal deterioration and amplifies the decline on measures of executive functioning (b) higher fitness levels augment the effects of shorter durations of hormone treatment and ameliorate the declines associated with prolonged hormone treatment.

Aged↗

PubMed2005

Selective sparing of brain tissue in postmenopausal women receiving hormone replacement therapy.

Determining the benefits and/or drawbacks of hormone replacement therapy (HRT) on women's health is an imperative public health goal. Research in rodents suggests benefits of estrogen on neuronal growth and function. However, little research has investigated the effects of HRT on brain tissue in humans. We used high-resolution magnetic resonance imaging and an optimized voxel-based morphometric technique to examine the effects of HRT on brain volume in postmenopausal women. We report two main results: (a) HRT is associated with the sparing of grey matter in prefrontal, parietal, and temporal brain regions and white matter in medial temporal lobe regions, and (b) longer durations of therapy are associated with greater sparing of grey matter tissue. HRT should be considered a possible mediator of age-related neural decline in both grey and white matter tissues.

Age Factors↗

PubMed2004

Role of estrogen in balancing contributions from multiple memory systems.

In addition to modulating memory per se, estrogen alters the learning strategy used to solve a task, thereby regulating the quality of information processed by the brain. This review discusses estrogen's actions on cognition within a memory systems framework, highlighting our work with a variety of paradigms showing that learning strategy is sensitive to estrogen even when learning rate is not. Specifically, high levels of gonadal steroids, in particular, elevations in estrogen, bias female rats toward using hippocampal-sensitive approaches while low levels of gonadal steroids promote the use of non-hippocampal sensitive strategies. In light of findings from a variety of approaches involving the hippocampus in allocentric and the striatum in egocentric response patterns, it is likely that estrogen alters the relative participation of these, and most undoubtedly other, neural systems during cognition. Changes in neuromodulators such as acetylcholine that regulate other processes such as inhibitory tone and excitability reflect one mechanism by which estrogen may orchestrate learning and memory.

Animals↗

PubMed2004

Acute stress impairs spatial memory in male but not female rats: influence of estrous cycle.

We investigated how sex and estrous cycle influenced spatial recognition memory in the Y-maze after exposure to acute restraint stress. In Experiment 1, intact male and female rats were restrained for 1 h and then 2 h after the start of restraint, rats were trained on the Y-maze. After a 4 h delay, hippocampal-dependent spatial recognition memory was assessed. Acute stress produced opposite patterns between the sexes with spatial memory being impaired in males and facilitated in females. Serum corticosterone measures indicated that both sexes showed a robust corticosterone response after restraint and a moderate corticosterone response after Y-maze exposure. Serum corticosterone levels in response to restraint and Y-maze were not statistically different between the sexes. Experiment 2 examined the influence of the estrous cycle on spatial memory ability after acute stress. Acute stress facilitated spatial memory in females compared to controls, regardless of the estrous cycle phase (estrus and proestrus). Moreover, females in proestrus showed higher serum corticosterone levels during restraint compared to females in estrus. No differences in corticosterone levels were observed at baseline or following 2 h of recovery from restraint. These data show important differences in how sex and estrous cycle influence cognitive functions following acute stress.

Acute Disease↗

PubMed2004

Shifts in preferred learning strategy across the estrous cycle in female rats.

The current status of the effects of ovarian steroids on learning and memory remains somewhat unclear, despite a large undertaking to evaluate these effects. What is emerging from this literature is that estrogen, and perhaps progesterone, influences learning and memory, but does so in a task-dependent manner. Previously, we have shown that ovariectomized rats given acute treatments of estrogen acquire allocentric or "place" tasks more easily than do rats deprived of estrogen, but acquire egocentric or "response" learning tasks more slowly than do those deprived of hormone, suggesting that estrogen treatment may bias the strategy a rat is able to use to solve tasks. To determine if natural fluctuations in ovarian hormones influence cognitive strategy, we tested whether strategy use fluctuated across the estrous cycle in reproductively intact female rats. We found that in two tasks in which rats freely choose the strategy used to solve the task, rats were more likely to use place strategies at proestrous, that is, when ovarian steroids are high. Conversely, estrous rats were biased toward response strategies. The data suggest that natural fluctuations in ovarian steroids may bias the neural system used and thus the cognitive strategies chosen during learning and memory.

Animals↗

PubMed2003

Dietary genistein results in larger MNU-induced, estrogen-dependent mammary tumors following ovariectomy of Sprague-Dawley rats.

Due to the estrogenic properties of soy-derived isoflavones, many postmenopausal women are using these compounds as a natural alternative to hormone replacement therapy (HRT). How isoflavones impact breast cancer in postmenopausal women is important, because a majority of breast cancer cases occur in this age group. Chemical induction of mammary tumors in female rats has been used to determine that exposure of the mammary gland to soy isoflavones prior to tumor induction is protective against tumor formation. Here we investigate the effect of dietary genistein on mammary tumors that have already formed. The study was designed to determine the action of dietary genistein in a low endogenous estrogen environment as is observed in postmenopausal women. Animals were ovariectomized (OVX) after mammary tumor development and were then placed into one of three treatment groups: positive-control (OVX+ estradiol implant), genistein (OVX+ 750 p.p.m. genistein) and negative-control (OVX alone). Tumors were distinguished as malignant or benign by histopathological examination and were further characterized as either estrogen-dependent or estrogen-independent using immunohistochemistry to identify the presence of both estrogen receptor (ER) alpha and the progesterone receptor (PR). Genistein at 750 p.p.m. increased the weight of estrogen-dependent adenocarcinomas in ovariectomized rats compared with the negative-control animals. Genistein treatment also resulted in a higher percentage of proliferative cells in tumors and increased uterine weights when compared with negative-control animals. Collectively, these effects are probably due to the estrogenic activity of genistein. Plasma genistein concentrations in animals fed the isoflavone-containing diet were at physiological levels relevant to human exposure. Estradiol concentrations in ovariectomized animals not receiving an estradiol supplement were similar to those observed in postmenopausal women. The data suggest that in an endogenous estrogen environment similar to that of a postmenopausal woman, dietary genistein can stimulate the growth of a mammary carcinogen MNU-induced estrogen-dependent mammary tumors.

Adenocarcinoma↗

PubMed2002

Estrogen-induced changes in place and response learning in young adult female rats.

Many findings suggest that changes in circulating estrogen levels influence cognition, in some cases impairing performance and in others enhancing performance. One interpretation of these mixed effects is that estrogen biases the strategy used to solve a task. To test this idea, young adult female rats, ovariectomized for 21 days, were trained after acute hormone or control treatment in 2 very similar tasks with different cognitive requirements. One task required place learning and the other response learning. Rats given two 10-microg injections of estradiol 48 and 24 hr before training learned the place task significantly faster than did rats without estradiol. Conversely, rats without estradiol performed better on the response task than did rats with replacement. These data suggest that the cognitive actions of estrogen may be task-specific by modulating the relative contribution of different learning and memory systems.

Aging↗

PubMed2002

Enhancing cognitive function across the life span.

Glucose administration regulates many neural and behavioral processes in rodents, including learning and memory. Given the important role of glucose in brain function and the safety of glucose as a treatment, we have investigated the effects of glucose administration in humans of different ages. In previous work, we examined the effects of early-morning glucose consumption on cognitive functions in elderly individuals. In this population, glucose enhanced performance on specific measures, particularly on those tasks where mild age-related deficits appear (e.g., verbal declarative memory). Interestingly, glucose failed to enhance cognitive functions in young adults. Our recent work has examined three issues related to glucose enhancement of cognition: First, is glucose effective only in reversing impairments or can it also facilitate performance in highly functioning individuals? Second, are glucose effects dependent either on time of day or on interactions with other meals? Third, are typical breakfast foods as effective as glucose in enhancing cognitive performance? Our findings suggest that glucose can improve memory in highly functioning populations as it does in populations with deficits. However, enhancement by glucose may require sufficient levels of task difficulty and of blood glucose. In addition, like glucose, early morning consumption of cereal can improve performance on some cognitive tests. These results have important implications for the nature of glucose facilitation of memory and for the role of dietary factors in performance of many daily activities.

Aging↗

PubMedDate not supplied

Intrahippocampal muscimol shifts learning strategy in gonadally intact young adult female rats.

Learning strategy preferences depend upon circulating estrogen levels, with enhanced hippocampus-sensitive place learning coinciding with elevated estrogen levels. The effects of estrogen on strategy may be mediated by fluctuations in GABAergic function, given that inhibitory tone in the hippocampus is low when estrogen is high. We investigated the effects on learning strategy of intrahippocampal injections of a GABA(A) agonist in gonadally intact female rats. On the day of training, rats received 0.3 microL intrahippocampal infusions of muscimol (0.26 nmol or 2.6 nmol) or saline 20 min prior to training on a T-maze in which place (hippocampus-sensitive) or response (striatum-sensitive) strategies offer effective solutions. Muscimol treatment increased the use of the response strategy in a dose-dependent manner without influencing learning speed, indicating that muscimol modulated strategy and not learning ability. Furthermore, the muscimol-related shift to response strategies varied across the estrous cycle. The results indicate that increasing inhibition in the hippocampus biases rats away from hippocampus-sensitive place learning strategies and toward hippocampus-insensitive response learning strategies without a learning deficit. Furthermore, rats at proestrus demonstrated the most dramatic shift in learning strategy following muscimol treatment compared with control conditions, while rats at estrus demonstrated the most complete bias toward response strategies. The enhanced use of hippocampus-sensitive strategies at proestrus likely results from reduced hippocampal inhibition.

Animals↗