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Articles 1 - 30 of 49
Full-Text Articles in Medicine and Health Sciences
Regulation Of The Mouse And Human Β-Globin Genes By Krüppel Like Transcription Factors Klf1 And Klf2, Yousef N. Alhashem
Regulation Of The Mouse And Human Β-Globin Genes By Krüppel Like Transcription Factors Klf1 And Klf2, Yousef N. Alhashem
Theses and Dissertations
Krüppel-like factors KLF1 and KLF2 are closely related transcription factors with three zinc finger domains in their carboxy-termini. KLF1 (erythroid Krüppel-like factor, or EKLF) plays essential roles in embryonic and adult erythropoiesis. KLF2 is a positive regulator of the mouse and human embryonic β- globin genes. KLF1 and KLF2 have overlapping roles in embryonic erythropoiesis, as demonstrated using single and double knockout (KO) mouse models. Ablation of the KLF1 or KLF2 gene causes embryonic lethality, and double KO embryos are more anemic and die sooner than either single KO. We have shown that KLF1 and KLF2 positively regulate the human …
From Linkage To Gwas: A Multifaceted Exploration Of The Genetic Risk For Alcohol Dependence, Amy Adkins
From Linkage To Gwas: A Multifaceted Exploration Of The Genetic Risk For Alcohol Dependence, Amy Adkins
Theses and Dissertations
Family, twin and adoption studies consistently suggest that genetic factors strongly influence the risk for alcohol dependence (AD). Although the literature supports the role of genetics in AD, identification of specific genes contributing to the etiology of AD has proven difficult. These difficulties are due in part to the complex set of risk factors contributing to the development of AD. These risk factors include comorbidities with other clinical diagnoses and behavioral phenotypes (e.g., major depression), physiological differences that contribute to the differences between people in their level of response to ethanol (e.g., initial sensitivity) and finally the large number of …
Diffuse Traumatic Axonal Injury Within The Visual System: Implications For Visual Pathway Reorganization, Jiaqiong Wang
Diffuse Traumatic Axonal Injury Within The Visual System: Implications For Visual Pathway Reorganization, Jiaqiong Wang
Theses and Dissertations
Traumatic brain injury is a major health problem with much of its morbidity associated with traumatic axonal injury (TAI). To date, significant insight has been gained into the initiating pathogenesis of TAI. However, the specific anterograde and retrograde sequelae of TAI are poorly understood because the diffuse nature of TAI complicates data analysis. To overcome this limitation, we subjected transgenic mice expressing yellow fluorescent protein (YFP) within the visual system to central fluid percussion injury, and consistently generated diffuse TAI within the optic nerve that could easily be followed in the organized YFP positive fibers. We demonstrated progressive axonal swelling, …
Role Of Tyrosyl-Dna Phosphodiesterase (Tdp 1) On Repair Of 3′-Phosphoglycolate (3′- Pg) Terminated Dna Double-Strand Breaks (Dsbs) And In Response To Oxidative Stress, Tong Zhou
Theses and Dissertations
DNA DSBs are most toxic to cells because they can lead to genomic rearrangements and even cell death. Most DSBs induced by ionizing radiation or radiomimetic drugs such as calicheamicin and bleomycin, bear 3′-phosphate or 3′- PG moieties that must be removed to allow subsequent gap filling and ligation. DSBs can be repaired by two main pathways: the homologous recombination (HR) pathway and the non-homologous end-joining (NHEJ) pathway, NHEJ is the primary repair pathway in mammalian cells. While HR repairs single strand breaks (SSBs) or DSBs accurately by using an undamaged copy of the sequence mostly at late S phase …
Investigating A Model For Fetal Alcohol Damage In Caenorhabditis Elegans, Lindsay Kondo
Investigating A Model For Fetal Alcohol Damage In Caenorhabditis Elegans, Lindsay Kondo
Theses and Dissertations
Alcohol use and abuse has many harmful effects, especially to children exposed prenatally, including fetal alcohol spectrum disorders (FASDs). The disabilities due to fetal alcohol exposure continue throughout life and cause major financial burdens to society. The molecular mechanisms underlying FASDs are not well understood. We have taken a genetic approach to characterize ethanol’s effect on changing a discrete cell fate decision during embryogenesis in the nematode, Caenorhabditis elegans (C. elegans). Our preliminary data suggest that ethanol can affect the development of AWC neurons, a pair of olfactory neurons in C. elegans. We suggest that lipids can protect AWC neurons …
The Role Of P62 In Osteoclastogenesis And Paget’S Disease Of Bone, Tamer Hadi
The Role Of P62 In Osteoclastogenesis And Paget’S Disease Of Bone, Tamer Hadi
Theses and Dissertations
Paget’s disease (PDB) is the second most common metabolic bone disease after osteoporosis, affecting up to 3% of adults over age 55. It is characterized by focal lesions of bone resorbed by hyperactive osteoclasts coupled with rapid formation of highly disorganized, low quality bone formed by osteoblasts. Such lesions cause skeletal deformity, fractures, and other symptoms that significantly decrease quality of life. In 2001, mutations in the SQSTM1/p62 gene were found in a subset of Paget’s patients. The work summarized in this dissertation sought to answer two broad questions: what is the function of p62 in normal bone homeostasis and …
The Role Of Magl Inhibition In Nicotine Withdrawal And Reward, Pretal Muldoon
The Role Of Magl Inhibition In Nicotine Withdrawal And Reward, Pretal Muldoon
Theses and Dissertations
ROLE OF MAGL INHIBITION IN NICOTINE WITHDRAWAL AND REWARD. A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University. by Pretal Ishvarlal Patel Muldoon Director: M. Imad Damaj, PhD Professor, Department of Pharmacology and Toxicology Tobacco use is one of the leading causes of preventable deaths worldwide. Nicotine, the main psychoactive component of tobacco, sustains and initiates tobacco addiction. Cessation of nicotine induces a dependence withdrawal syndrome. Recent in vivo studies indicate that the endocannabinoid (EC) system modulates both nicotine reward and withdrawal. The purpose of this proposal is to …
On The Genetic And Environmental Associations Between Body Composition, Depression Symptoms And Smoking Behavior., Roseann Peterson
On The Genetic And Environmental Associations Between Body Composition, Depression Symptoms And Smoking Behavior., Roseann Peterson
Theses and Dissertations
Obesity is a serious public health crisis and recent estimates of its incidence are the highest in United States history, with 35% and 17% of American adults and children affected, respectively. The clinical definition of adult obesity is operationalized as a body mass index (BMI) greater than 30 kg/m2. Although the prevalence of common obesity has increased dramatically over the past 30 years–largely thought to be due to changes in the environment, such as high calorie diets and sedentary lifestyles—twin and family studies have shown consistently that relative body weight is under considerable genetic influence in both children and adults, …
Examining Alcohol Dependence And Its Correlates From A Genetically Informative Perspective, Laura Hack
Examining Alcohol Dependence And Its Correlates From A Genetically Informative Perspective, Laura Hack
Theses and Dissertations
Alcohol dependence (AD) is a serious and common public health problem that contributes to great societal, medical, and legal costs. It has taken work from multiple disciplines, including developmental psychology, genetic epidemiology, and molecular genetics, to achieve our current understanding of environmental and genetic risk factors for AD as well as its variable developmental trajectories. Nevertheless, there is still much to be learned in order to improve treatment outcomes. One approach to augmenting our understanding of this disorder is through genetically informative study designs that either examine risk in aggregate or assess specific susceptibility variants. In this dissertation, we utilize …
Using Genetic Information In Risk Prediction For Alcohol Dependence, Jia Yan
Using Genetic Information In Risk Prediction For Alcohol Dependence, Jia Yan
Theses and Dissertations
Family-based and genome-wide association studies (GWAS) of alcohol dependence (AD) have reported numerous associated variants. The clinical validity of these variants for predicting AD compared to family history has not yet been reported. These studies aim to explore the aggregate impact of multiple genetic variants with small effect sizes on risk prediction in order to provide a clinical interpretation of genetic contributions to AD. Data simulations showed that given AD’s prevalence and heritability, a risk prediction model incorporating all genetic contributions would have an area under the receiver operating characteristic curve (AUC) approaching 0.80, which is often a target AUC …
Role Of Autophagy In The Response Of Hs578t Breast Tumor Cells To Radiation, Shweta Chakradeo
Role Of Autophagy In The Response Of Hs578t Breast Tumor Cells To Radiation, Shweta Chakradeo
Theses and Dissertations
Breast cancer is the most commonly observed cancer type in women and is the second leading cause of cancer death in women. Radiation can be used to debulk tumors prior to surgery as well as to treat patients after surgery and/or chemotherapy. Previous studies from our laboratory have shown that the anti –malarial drug chloroquine sensitizes breast cancer cell lines to radiation by suppression of autophagy which is a conservative catabolic process that can be cytoprotective. The scientific literature has demonstrated that many tumor cell systems undergo cytoprotective autophagy and that pharmacological or genetic inhibition of autophagy leads to other …
Role Of Nicotinic Acetylcholine Receptors In Experimental Colitis, Shakir Alsharari
Role Of Nicotinic Acetylcholine Receptors In Experimental Colitis, Shakir Alsharari
Theses and Dissertations
Substantial evidence in the literature shows that tobacco smoking has complex and divergent effects on inflammatory bowel diseases (IBD). It ameliorates ulcerative colitis (UC); whereas it aggravates the risk of Crohn’s disease (CD) and affects the disease course and severity. Studies have shown that nicotine has a positive influence on symptoms of UC. Also, it is demonstrated that nicotinic acetylcholine receptor, especially α7 subunit plays an essential component in the vagus nerve-based cholinergic anti-inflammatory effects. In the present study, we explored the effect of nicotine and α7 nicotinic agonists treatment in the DSS colitis mouse model. We also investigated the …
Development Of Natural Cyclic Peptide Inhibitors Of Xrcc4/Xlf Interaction For Radio-Sensitization Of Breast Tumor Cells, Mohaini Mohammed Al
Development Of Natural Cyclic Peptide Inhibitors Of Xrcc4/Xlf Interaction For Radio-Sensitization Of Breast Tumor Cells, Mohaini Mohammed Al
Theses and Dissertations
Breast cancer is the second leading cause of cancer death in women according to the American Cancer Society. The standard treatment regimen for breast cancer involves ionizing radiation combined with surgery and chemotherapy. Ionizing radiation induces a complex signaling response in cells resulting in either growth arrest, senescence or cell death, and the cell killing after exposure to radiation results largely from DNA double-strand breaks (DSBs). There are two main mechanisms in mammalian cells responsible for repairing the DSBs; the primary mechanism is non-homologous end joining (NHEJ) and the secondary mechanism is homologous recombination (HRR). Previous studies showed that breast …
Cell Death And Growth Arrest Pathways Mediating The Actions Of Stilbene 5c In Hct-116 Colon Cancer Cells, Moureq Alotaibi
Cell Death And Growth Arrest Pathways Mediating The Actions Of Stilbene 5c In Hct-116 Colon Cancer Cells, Moureq Alotaibi
Theses and Dissertations
Abstract The stilbene derivative, cis-3, 4’, 5-trimethoxy-3’-aminostilbene (stilbene 5c), is a potentially potent antitumor agent that acts via binding to the colchicine-binding pocket in microtubules. Earlier studies have shown that stilbene 5c induces cell death in ovarian cancer cells and leukemic cells. The present study was designed to investigate the effectiveness of this microtubule poison against the HCT-116 human colon cancer cell line and its mechanisms of action. Time course studies demonstrated that stilbene 5c produces a biphasic decrease in cell viability. The capacity of the cells to proliferate was not restored upon removal of the drug after 6 days …
Role Of Nucleosome Remodeling Factor (Nurf) In Tumorigenesis Using A Breast Cancer Mouse Model, Aiman Alhazmi
Role Of Nucleosome Remodeling Factor (Nurf) In Tumorigenesis Using A Breast Cancer Mouse Model, Aiman Alhazmi
Theses and Dissertations
Understanding the impact of epigenetic mechanisms on tumorigenesis is essential, as epigenetic alterations are associated with tumor initiation and progression. Because epigenetic changes are reversible, they are potential targets for cancer therapy. Nucleosome Remodeling Factor (NURF) is a chromatin-remodeling complex that regulates gene expression by changing nucleosome positioning along the DNA sequence. Previous studies have shown a role for NURF in embryonic development as well as regulating genes involved in tumor progression. In this work we investigated the impact of eliminating NURF function in tumorigenesis in vivo. BALB/c mice challenged with syngeneic 67NR breast cancer cell lines, injected into the …
The Role Of Tetraspanin-8 In Astrocyte Elevated Gene-1 Mediated Progression Of Hepatocellular Carcinoma, Maaged Akiel
The Role Of Tetraspanin-8 In Astrocyte Elevated Gene-1 Mediated Progression Of Hepatocellular Carcinoma, Maaged Akiel
Theses and Dissertations
Hepatocellular carcinoma (HCC) is a devastating form of liver cancer that accounts for 80% of liver cancers. HCC has a poor prognosis with five-year survival of less than 12% in the United States. We in previous studies have identified Astrocyte Elevated Gene-1 (AEG-1) as an aberrantly overexpressed gene in many cancers including HCC, regulating tumor progression. Microarray studies identified the small transmembrane protein, tetraspanin8 (TSPAN8) as a downstream of AEG-1. TSPAN8 belongs to the family of TETRASPANINS with the characteristic of crossing the membrane four times, and regulating a wide range of cellular phenomena. TSPAN8 is implicated in metastasis and …
Characterizing The Role Of Nucleosome Remodeling Factor (Nurf) In Tumorigenesis And Metastatic Progression Using Mouse Models Of Breast Cancer., Suehyb Alkhatib
Characterizing The Role Of Nucleosome Remodeling Factor (Nurf) In Tumorigenesis And Metastatic Progression Using Mouse Models Of Breast Cancer., Suehyb Alkhatib
Theses and Dissertations
Increasingly the role of epigenetic machinery as a bridge between underlying DNA sequence and cellular phenotype is being discovered. The establishment of a myriad of unique cellular types sharing identical gene sequences in a multicellular organism gives a broad sense for the inherent role of epigenetic influence on cell differentiation. Importantly, the epigenetic mechanisms involved in establishing cell identity unsurprisingly contribute to diseased states, including cancer. Recent research continues to elucidate contributory roles of epigenetic mechanisms, such as DNA methylation, histone modification, and microRNA regulation, in human cancers. Additionally, chromatin remodelers, such as the Nucleosome Remodeling Factor (NURF), have been …
Elucidating Genetic And Environmental Influences On Alcohol-Related Phenotypes, Jacquelyn Meyers
Elucidating Genetic And Environmental Influences On Alcohol-Related Phenotypes, Jacquelyn Meyers
Theses and Dissertations
Decades of work has led researchers to believe that risk for complex behavioral phenotypes, such as alcohol use disorders, is likely influenced by multiple genes of small effect acting in conjunction with each other and the environment. Currently, the field of psychiatric genetics is developing methodologies for the identification of genetic risk variants that predispose individuals to the development of complex behavioral disorders. Several challenges related to the complex and polygenic nature of these phenotypes, must be considered. This dissertation study attempts to address these important challenges in the context of alcohol use disorders and related phenotypes. A rich twin …
Unique Features And Neuronal Properties In A Multisensory Cortex, W. Alex Foxworthy
Unique Features And Neuronal Properties In A Multisensory Cortex, W. Alex Foxworthy
Theses and Dissertations
UNIQUE FEAUTRES OF ORGANIZATION AND NEURONAL PROPERTIES IN A MULTISENSORY CORTEX Multisensory processing is a ubiquitous sensory effect that underlies a wide variety of behaviors, such as detection and orientation, as well as perceptual phenomena from speech comprehension to binding. Such multisensory perceptual effects are presumed to be based in cortex, especially within areas known to contain multisensory neurons. However, unlike their lower-level/primary sensory cortical counterparts, little is known about the connectional, functional and laminar organization of higher-level multisensory cortex. Therefore, to examine the fundamental features of neuronal processing and organization in the multisensory cortical area of the posterior parietal …
Otx But Not Mitf Transcription Factors Are Required For Zebrafish Rpe Development, Brandon Lane
Otx But Not Mitf Transcription Factors Are Required For Zebrafish Rpe Development, Brandon Lane
Theses and Dissertations
Mitf and Otx transcription factors have been identified as essential to the development of the retinal pigmented epithelium (RPE), but the relationship between these factors and their specific role in the RPE developmental pathway have not been clearly defined. The role of the two Mitf transcription factors (Mitfa and Mitfb) and two Otx transcription factors (Otx1a and Otx2) in zebrafish RPE development was explored in these experiments. The loss of Mitf activity in mitfa, mitfb, or double mitf null mutant fish lines had no effect on RPE pigmentation or development. The loss of Otx2 activity through morpholino knockdown produced a …
The Antinociceptive Effects Of Alpha 7 Nicotinic Acetylcholine Receptor Positive Allosteric Modulators In Different Animal Pain Models, Kelen Freitas
The Antinociceptive Effects Of Alpha 7 Nicotinic Acetylcholine Receptor Positive Allosteric Modulators In Different Animal Pain Models, Kelen Freitas
Theses and Dissertations
The α7 nicotinic acetylcholine receptor (nAChR) subtype is abundantly expressed in the central nervous system (CNS) and in the periphery. Positive allosteric modulators (PAMs) of the α7 increase the response to an agonist and are divided into two types depending on whether they also decrease desensitization of the receptor (type II) or not (type I). Therefore, this study aims to investigate whether the enhancement of endogenous α7 nAChR function will result in a beneficial effect in nociceptive, inflammatory and chronic neuropathic pain models. While NS1738 and PNU-120596 were not active to reduce acute thermal pain, measured by hot-plate and tail-flick …
Function Of Insulin-Like Growth Factor Binding Protein 7 (Igfbp7) In Hepatocellular Carcinoma, Dong Chen
Function Of Insulin-Like Growth Factor Binding Protein 7 (Igfbp7) In Hepatocellular Carcinoma, Dong Chen
Theses and Dissertations
Title of Dissertation: FUNCTION OF INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN 7(IGFBP7) IN HEPATOCELLULAR CARCINOMA By Dong Chen. Purpose: Hepatocellular carcinoma (HCC) is a highly virulent malignancy with no effective treatment, thus requiring the development of innovative and effective targeted therapies. The oncogene Astrocyte Elevated Gene-1 (AEG-1) plays a seminal role in hepatocarcinogenesis and profoundly downregulates Insulin-like Growth Factor Binding Protein-7 (IGFBP7). The present study focuses on analyzing potential tumor suppressor functions of IGFBP7 in HCC and the relevance of IGFBP7 downregulation in mediating AEG-1 function. Experimental Design: IGFBP7 expression was detected by immunohistochemistry in HCC tissue microarrays by real-time PCR …
Radiation Sensitization Of Breast Cancer Cells By Vitamin D Through The Promotion Of Autophagic Cell Death, Eden Wilson
Radiation Sensitization Of Breast Cancer Cells By Vitamin D Through The Promotion Of Autophagic Cell Death, Eden Wilson
Theses and Dissertations
Radiation therapy is a widely used tool in cancer therapy and is frequently offered as the first line of treatment for cancers of the breast. While radiotherapy is often initially effective in killing tumor cells or suppressing their growth, there are factors that confer tumor cell resistance to irradiation. Development of resistance may lead to disease recurrence despite the use of surgery, chemotherapy and radiation therapy. A primary goal of the studies in Dr. Gewirtz’s laboratory is to develop strategies to overcome resistance to radiation (and chemotherapy) in breast cancer, with the ultimate goal of preventing or attenuating disease recurrence. …
Tgf-Beta Receptors And Alcohol Sensitivity In Drosophila, Kristyn Sennett
Tgf-Beta Receptors And Alcohol Sensitivity In Drosophila, Kristyn Sennett
Theses and Dissertations
Clic proteins influence ethanol-related behavior in flies and other species and also mediate TGF-β signaling. These findings suggest that Clics and the TGF-β signaling pathway might work together to modulate behavioral responses to ethanol. I used the Drosophila model to address the hypothesis that TGF-β signaling is important for ethanol sensitivity. Ethanol sensitivity was blunted by multiple transposon insertions in the TGF-β receptor gene thickveins. Collectively, however, I found no consistent correlation between expression of thickveins and altered ethanol sensitivity in flies harboring transposons. I therefore also assessed ethanol sensitivity in flies with loss of function point mutations in thickveins. …
Hydrogen Sulfide As An Allosteric Modulator Of Atp Sensitive Potassium Channels In Colonic Inflammation., Aravind Gade
Hydrogen Sulfide As An Allosteric Modulator Of Atp Sensitive Potassium Channels In Colonic Inflammation., Aravind Gade
Theses and Dissertations
The ATP sensitive potassium channel (KATP) in mouse colonic smooth muscle cell is a complex containing a pore forming subunit (Kir6.1) and a sulfonyl urea receptor subunit (SUR2B). These channels are responsible for maintaining the cellular excitability of the smooth muscle cell which in turn regulates the motility patterns in the colon. We used whole-cell voltage-clamp techniques to study the alterations in these channels in smooth muscle cells in experimental model of colitis (colonic inflammation). Colitis was induced in BALB/C mice following an intracolonic administration of trinitrobenzene sulfonic acid (TNBS). KATP currents were measured at Vh -60 mV in high …
Overexpression Of Serum Response Factor In Astrocytes Improves Neuronal Plasticity In A Model Of Fetal Alcohol Spectrum Disorders, Arco P. Paul
Theses and Dissertations
Neuronal plasticity deficits underlie many of the neurobehavioral problems seen in Fetal Alcohol Spectrum Disorders (FASD). Recently, we showed that third trimester alcohol exposure lead to a persistent disruption in ocular dominance (OD) plasticity. For instance, few days of monocular deprivation results in a robust reduction of cortical regions responsive to the deprived eye in normal animals, but not in ferrets exposed early to alcohol. This plasticity deficit can be reversed if alcohol-exposed animals are treated with a phosphodiesterase type 1 (PDE1) inhibitor during the period of monocular deprivation. PDE1 inhibition can increase cAMP and cGMP levels, activating transcription factors …
Myelin Gene Expression: Implications For Alcohol Abuse And Dependence, Sean Farris
Myelin Gene Expression: Implications For Alcohol Abuse And Dependence, Sean Farris
Theses and Dissertations
Acute behavioral responses to ethanol have predictive value for determining an individual's risk of long-term drinking behavior. Although the neurobiology of alcohol abuse is complex, prior studies from our laboratory demonstrated differential myelin-associated gene expression (MAGE) in medial prefrontal cortex (PFC) as one potential mechanism influencing acute ethanol behaviors between C57BL/6J (B6) and DBA/2J (D2) mice. Our laboratory and others have also shown MAGE is reduced in PFC of alcoholics. Herein, I have extended these findings through expression profiling of PFC into chronic models of ethanol self-administration from non-human primates and mice. Together, these results suggest that regulation of MAGE …
Antinociceptive Effects Of Monoamine Reuptake Inhibitors In Assays Of Pain-Stimulated And Pain-Depressed Behaviors, Marisa Rosenberg
Antinociceptive Effects Of Monoamine Reuptake Inhibitors In Assays Of Pain-Stimulated And Pain-Depressed Behaviors, Marisa Rosenberg
Theses and Dissertations
ANTINOCICEPTIVE EFFECTS OF MONOAMINE REUPTAKE INHIBITORS IN ASSAYS OF PAIN-STIMULATED AND PAIN-DEPRESSED BEHAVIOR By Marisa B. Rosenberg A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science at Virginia Commonwealth University. Virginia Commonwealth University, 2012 Advisor: Sidney Stevens Negus, Ph.D. Professor, Department of Pharmacology/Toxicology Noxious stimuli can produce pain-related stimulation of some behaviors (e.g. withdrawal responses) and depression of other behaviors (e.g. feeding, locomotion, responding maintained by many types of positive reinforcement). Monoamine reuptake inhibitors are used clinically to treat depression and to manage some types of pain. This study examined the antinociceptive properties …
Elevating Endogenous Cannabinoids Reduces Opioid Withdrawal In Mice, Divya Ramesh
Elevating Endogenous Cannabinoids Reduces Opioid Withdrawal In Mice, Divya Ramesh
Theses and Dissertations
Delta9-tetrahydrocannbinol (THC), the primary active constituent of Cannabis sativa, has long been known to reduce opioid withdrawal symptoms. Although THC produces most of its pharmacological actions through the activation of CB1 and CB2 cannabinoid receptors, the role these receptors play in reducing opioid withdrawal symptoms remains unknown. The endogenous cannabinoids, N-arachidonoylethanolamine (anandamide; AEA) and 2-arachidonylglycerol (2-AG), activate both cannabinoid receptors, but are rapidly metabolized by fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), respectively. The objective of this dissertation was to test whether increasing AEA or 2-AG, via inhibition of their respective hydrolytic enzymes, reduces morphine withdrawal symptoms in …
The Role Of Calcineurin In Dendritic Remodeling And Epileptogenesis In A Rat Model Of Traumatic Brain Injury, John Campbell
The Role Of Calcineurin In Dendritic Remodeling And Epileptogenesis In A Rat Model Of Traumatic Brain Injury, John Campbell
Theses and Dissertations
Traumatic brain injury (TBI), a leading cause of death and disability in the United States, causes potentially preventable damage in part through the dysregulation of neural calcium levels. This dysregulation likely affects the activity of the calcium-sensitive phosphatase, calcineurin, with serious implications for neural function. To test this possibility, the present study characterized the role of calcineurin in a rat model of brain trauma, the lateral fluid percussion injury model. Golgi-Cox histochemistry revealed an acute post-TBI loss and delayed overgrowth of dendritic spines on principal cortical cells. The spine loss appeared to require calcineurin activity, since administering a calcineurin inhibitor, …