Melinda E Wilson

Melinda E Wilson
University of Kentucky | UKY · Department of Physiology

PhD

About

40
Publications
3,013
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3,356
Citations
Citations since 2017
0 Research Items
634 Citations
2017201820192020202120222023020406080100120
2017201820192020202120222023020406080100120
2017201820192020202120222023020406080100120
2017201820192020202120222023020406080100120
Introduction
Skills and Expertise

Publications

Publications (40)
Article
Reactivation of chronic infection with Toxoplasma gondii can cause life-threatening toxoplasmic encephalitis in immunocompromised individuals. We examined the role of VCAM-1/α4β1 integrin interaction in T cell recruitment to prevent reactivation of the infection in the brain. SCID mice were infected and treated with sulfadiazine to establish a chro...
Article
Stroke is a significant cause of death and long-term disability in the USA. The incidence, mortality, and outcomes of stroke are significantly different between men and women. As with many diseases that affect men and women differently, an understanding on the reasons underlying those differences is critical to effective diagnosis and treatment. Th...
Article
Steroid hormones have wide-ranging organizational, activational and protective actions in the brain. In particular, the organizational effects of early exposure to 17β-estradiol (E2) and glucocorticoids are essential for long-lasting behavioral and cognitive functions. Both steroid hormones mediate many of their actions through intracellular recept...
Article
Estrogens have many functions in the developing rodent brain, and most of these depend on the presence of estrogen receptors. Understanding how expression of these receptors are regulated is crucial for understanding the roles of estradiol in the male and female brain during development In rodents, the prefrontal cortex (PFC) has been shown to be i...
Article
During aging, there is an increase in neurodegenerative diseases and a decrease in cognitive performance. Postmenopausal women are more vulnerable as their estrogen levels decline, but most hormone replacement therapies do not prevent cognitive decline. One potential reason is that the timing of hormone replacement is critical and changes in the es...
Article
17β-estradiol is a hormone with far-reaching organizational, activational and protective actions in both male and female brains. The organizational effects of early estrogen exposure are essential for long-lasting behavioral and cognitive functions. Estradiol mediates many of its effects through the intracellular receptors, estrogen receptor-alpha...
Article
Estrogens play a critical role in brain development by acting on areas that express estrogen receptors. In the rodent cortex, estrogen receptor alpha (ER alpha) mRNA expression is high early in postnatal development but declines starting at postnatal day (PND) 10 and is virtually absent in the adult cortex. The mechanisms controlling this regulatio...
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Full-text available
Many human immunodeficiency virus (HIV) proteins including Tat are produced by HIV-infected astrocytes and secreted into the brain resulting in extensive neuronal damage that contributes to the pathogenesis of HIV dementia. The neuroprotective hormone 17beta-estradiol (E2) is known to negatively regulate the HIV transcriptional promoter in human fe...
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Full-text available
Epigenetic changes in the nervous system are emerging as a critical component of enduring effects induced by early life experience, hormonal exposure, trauma and injury, or learning and memory. Sex differences in the brain are largely determined by steroid hormone exposure during a perinatal sensitive period that alters subsequent hormonal and nonh...
Article
17Beta-oestradiol is a pleiotropic hormone with organisational, activational and protective actions in both male and female mammals. It is responsible for numerous aspects of brain development, including sexual differentiation of the brain. The organisational effects of early oestrogen exposure are essential for long-lasting cognitive and behaviour...
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Full-text available
The peroxisome proliferator-activated receptor gamma 1 (PPARgamma1) is a nuclear receptor that plays a pivotal role in breast cancer and is highly over-expressed relative to normal epithelia. We have previously reported that the expression of PPARgamma1 is mediated by at least six distinct promoters and expression in breast cancer is driven by a tu...
Article
Estrogen has long been known to play an important role in coordinating the neuroendocrine events that control sexual development, sexual behavior and reproduction. Estrogen actions in other, non-reproductive areas of the brain have also been described. It is now known that estrogen can also influence learning, memory, and emotion and has neurotroph...
Article
Permanent middle cerebral artery occlusion (MCAO) causes neuronal cell death in the striatum and cortex. In rodents, estradiol treatment protects the cortex from cell death in an estrogen receptor alpha (ERalpha) dependent manner. ERalpha is only transiently expressed in the cortex during neonatal development and is very low in uninjured adult cort...
Article
Individuals with HIV can now live long lives with drug therapy that often includes protease inhibitors such as ritonavir. Many patients, however, develop negative long-term side effects such as premature atherosclerosis. We have previously demonstrated that ritonavir treatment increases atherosclerotic lesion formation in male mice to a greater ext...
Article
Recent attention has been given to gender differences in neurotrauma, and the anecdotal suggestion is that females have better outcomes than males, suggesting that circulating levels of estrogen (E(2)) may be neuroprotective. In order to address this issue, both young adult male and ovariectomized female rats were subjected to a T10 spinal cord inj...
Article
Estrogen plays a critical role in brain development and is responsible for generating sex differences in cognition and emotion. Studies in rodent models have shown high levels of estrogen binding in non-reproductive areas of the brain during development, including the cortex and hippocampus, yet binding is diminished in the same areas of the adult...
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Full-text available
Protease inhibitors, as part of highly active anti-retroviral therapy (HAART), have significantly increased the lifespan of human immunodeficiency virus (HIV) infected patients. Several deleterious side effects including dyslipidemia and lipodystrophy, however, have been observed with HAART. Women are at a higher risk of developing adipose tissue a...
Article
As epidemiological data have suggested that female patients may have improved clinical prognoses following traumatic brain injury (TBI) compared to males, we designed experiments to determine the role of gender and estrogen in TBI-induced brain injury and inflammation in rodents. To this end, male and female C57Bl/6 mice were separated into the fol...
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Full-text available
HIV protease inhibitors are important pharmacological agents used in the treatment of HIV-infected patients. One of the major disadvantages of HIV protease inhibitors is that they increase several cardiovascular risk factors, including the expression of CD36 in macrophages. The expression of CD36 in macrophages promotes the accumulation of choleste...
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Full-text available
The present study sought to determine whether chemical destruction of peripheral catecholaminergic fibers with 6-hydroxydopamine (6OHDA) attenuates vasopressin (VP) and oxytocin (OT) secretion stimulated by hemorrhage, hypotension, and hyperosmolality. Rats received 6OHDA (100 mg/kg iv) or vehicle (1 ml/kg iv) on days 1 and 7, and experiments were...
Article
Experimental and epidemiological data suggest that estrogen can be protective in both brain injury and infection. While estrogens can act directly on neurons to promote neuronal survival, estrogen also has antiinflammatory properties that may contribute to overall neuroprotection. Accordingly, estrogens may have particular relevance in chronic neur...
Article
HIV-associated dementia results from neuronal loss and an alteration of neuronal function due to a loss of synapses. While HIV infection in astrocytes is limited, astrocytes exhibit a chronic nonproductive infection that can lead to the release of neurotoxic proteins. Additionally, infection can disrupt the normal neurotrophic role of astrocytes th...
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Full-text available
As part of highly active antiretroviral therapy, protease inhibitor treatment has significantly increased the lifespan of human immunodeficiency virus (HIV)-infected individuals. Many patients, however, develop negative side effects, including premature atherosclerosis. We have previously demonstrated that in male low density lipoprotein receptor (...
Article
To model the effects of estrogen on adaptive immunity in the brain, we examined the effects of 17beta-estradiol on microglial parameters related to antigen presentation and T cell activation. Specifically, the effects of 17beta-estradiol on basal and LPS-induced surface staining of Class I and II MHC, as well as CD40, CD80, CD86, CD152, CD28, CD8,...
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Full-text available
Protease inhibitors decrease the viral load in HIV patients, however the patients develop hypertriglyceridemia, hypercholesterolemia, and atherosclerosis. It has been assumed that protease inhibitor-dependent increases in atherosclerosis are secondary to the dyslipidemia. Incubation of THP-1 cells or human PBMCs with protease inhibitors caused upre...
Article
We have previously demonstrated that estradiol reduces cell death in cortical explant cultures following injury induced by metabolic inhibition in a receptor-dependent fashion. In this study, we examined whether cell death involves apoptosis and assessed the potential mediators of estradiol's actions. Cortical explant cultures were generated from p...
Article
Estradiol's ability to influence neurochemical events that are critical to female reproductive cyclicity and behavior decreases with age. We tested the hypothesis that decreases in estrogen receptor-alpha (ERalpha) and/or ERbeta mRNA explain the brain's declining responsiveness to estradiol. We assessed ERalpha and ERbeta mRNA levels in intact and...
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Full-text available
The menopause marks the end of a woman's reproductive life. During the postmenopausal period, plasma estrogen concentrations decrease dramatically and remain low for the rest of her life, unless she chooses to take hormone replacement therapy. During the past 20 years, we have learned that changes in the central nervous system are associated with a...
Article
We have shown that 17beta-estradiol exerts profound protective effects against stroke-like ischemic injury in female rats. These effects are evident using physiological levels of estradiol replacement in ovariectomized rats and require hormone treatment prior to the time of injury. The protective actions of estradiol appear to be most prominent in...
Article
Full-text available
An accumulating body of evidence clearly establishes that estradiol is a potent neuroprotective and neurotrophic factor in the adult: it influences memory and cognition, decreases the risk and delays the onset of neurological diseases such as Alzheimer's disease, and attenuates the extent of cell death that results from brain injuries such as cereb...
Article
Our appreciation that estrogens are important neurotrophic and neuroprotective factors has grown rapidly. Although a thorough understanding of the molecular and cellular mechanisms that underlie this effect requires further investigation, significant progress has been made due to the availability of animal models in which we can test potential cand...
Article
Estradiol has been shown to exert trophic and protective actions in the brain. Our laboratory has shown that in vivo, low physiological levels of estradiol protect the female rat brain against ischemic injury. In the present study, we used organotypic cortical explant cultures to begin to decipher the mechanisms of estradiol's actions. Injury was i...
Article
Many clinical studies suggest that estrogen enhances memory and cognition and protects against neurodegenerative diseases and injury associated with stroke or stress. These results are strongly supported by experiments performed in animal models using both in vivo and in vitro methods. We present here data from our lab that establishes that physiol...
Article
In recent years our appreciation that estradiol is truly a pleiotropic hormone has grown dramatically. We will review the findings that suggest that estrogens may exert important non-reproductive actions on the brain. These studies provide important insights into the clinical effects of estrogen replacement therapy on age- and disease-related proce...
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Full-text available
We have shown that physiological levels of estradiol exert profound protective effects on the cerebral cortex in ischemia induced by permanent middle cerebral artery occlusion. The major goal of this study was to begin to elucidate potential mechanisms of estradiol action in injury. Bcl-2 is a proto-oncogene that promotes cell survival in a variety...
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Full-text available
In summary, the evidence that both the ovary and the brain are key pacemakers in the menopause is compelling. Our appreciation that estrogens are important neurotrophic and neuroprotective factors has grown rapidly. Future studies will allow us to better understand the ensemble of factors that interact to maintain regular reproductive cyclicity and...
Article
We are interested in how neuropeptides that regulate both food intake and reproductive function change with age and how life-prolonging moderate caloric restriction may influence the expression of these neuropeptides. We measured neuropeptide Y (NPY) and proopiomelanocortin (POMC) mRNA in the arcuate nucleus (AN), and galanin (GAL) mRNA in the AN,...

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