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Articles 1 - 23 of 23
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Interactions Among Sex, Apolipoprotein E Genotype, And 17-Beta Estradiol In A Mouse Model Of Alzheimer's Disease, Lisa Taxier
Interactions Among Sex, Apolipoprotein E Genotype, And 17-Beta Estradiol In A Mouse Model Of Alzheimer's Disease, Lisa Taxier
Theses and Dissertations
Alzheimer’s disease (AD) is the most common form of dementia, yet its cause remains a mystery and no truly effective treatments exist. The high incidence of AD, coupled with its devastating health and economic impacts, highlight the urgent need for continued research into the etiology of this disease (Ernst & Hay, 1994; Rice et al., 1993). Although existing and efficacious treatments for AD are lacking, several risk factors for AD have been identified. One such factor is apolipoprotein E genotype, which is the greatest genetic risk factor for AD (Ertekin-Taner, 2007; van der Flier et al., 2011). Another factor is …
Effect Of Neighborhood Socioeconomic Disadvantage On Brain Functional Connectivity And Structural Properties In Trauma-Exposed Adults, Elisabeth Kathleen Webb
Effect Of Neighborhood Socioeconomic Disadvantage On Brain Functional Connectivity And Structural Properties In Trauma-Exposed Adults, Elisabeth Kathleen Webb
Theses and Dissertations
Though there has been substantial progress towards understanding brain-behavior relationships and characterizing the neurobiology of psychiatric disorders, research has not translated as expected into novel prevention and treatment of mental health conditions. One limitation may be the emphasis on individual-level variables (e.g., income) and omission of relevant area-level factors (e.g., neighborhood socioeconomic disadvantage). Recently, attention has been directed towards identifying the biological mechanisms by which neighborhoods impact mental health. The chronic stress associated with living in a disadvantaged neighborhood promotes a cascade of maladaptive events, which in turn impact brain structure and functioning. The processes affected by chronic neighborhood stressors …
Anti-Angiogenic Effects Of Chemotherapeutic Agents And Their Enhancement With Ot-515 And S-Nach, Shimaa Adel Heikal
Anti-Angiogenic Effects Of Chemotherapeutic Agents And Their Enhancement With Ot-515 And S-Nach, Shimaa Adel Heikal
Theses and Dissertations
Chemotherapeutic agents have been used for the treatment of numerous types of tumors with great success. Cisplatin and Doxorubicin are among the well-known chemotherapeutic drugs that showed efficacy against various types of cancers. However, cell resistance and major side effects like chemotherapy-induced peripheral neuropathy (CIPN) are limiting factors in using these compounds. Using a combination or adjuvant compounds with anti-angiogenic effects is one of the strategies suggested to decrease resistance or ameliorate chemotherapeutic toxicity. The present study investigated the anti-angiogenic effects of Cisplatin and Doxorubicin alone and combined with Sulfated non-anticoagulant heparin (S-NACH), a low molecular weight heparin LMWH that …
Resting State Functional Connectivity In The Default Mode Network: Relationships Between Cannabis Use, Gender, And Cognition In Adolescents And Young Adults, Megan Ritchay
Theses and Dissertations
Introduction: Cannabis is the most commonly used illicit substance in the United States, and nearly 1 in 4 young adults are current cannabis users. The psychoactive component of cannabis, THC, is active at cannabinoid receptors, type 1, or CB1 receptors. CB1 receptors play a critical role in neural development, and chronic cannabis use causes desensitization and downregulation of these receptors. Chronic cannabis use is associated with changes in resting state functional connectivity (RSFC) in the default mode network (DMN) in adolescents and young adults, although results are somewhat inconsistent across studies, likely due to differing methodologies. Additionally, cannabis effects appear …
Effects Of A Novel, Non-Toxic Histone Deacetylase Inhibitor On Hippocampal Memory Formation, Histone Acetylation, And Bdnf Gene Expression In Male Mice, Sarah Brianna Beamish
Effects Of A Novel, Non-Toxic Histone Deacetylase Inhibitor On Hippocampal Memory Formation, Histone Acetylation, And Bdnf Gene Expression In Male Mice, Sarah Brianna Beamish
Theses and Dissertations
Memory dysfunction is a common symptom of aging, neuropsychiatric disorders, and neurodegenerative disorders, yet truly effective treatments for memory loss do not exist. De novo gene transcription is a molecular requirement for long-term memory formation. The transcription of genes related to synaptic plasticity and learning are regulated in part by histone acetylation, an epigenetic mechanism that regulates chromatin accessibility. Pharmacological compounds that maintain histone acetylation, called histone deacetylase inhibitors (HDACi), enhance memory by preventing deacetylation of core histone proteins, which initiates binding of transcriptional machinery to open chromatin. Therefore, HDACi are potentially promising therapeutics that could be used to prevent …
Resting-State Versus Breath-Hold For Testing Functional Magnetic Resonance Imaging Integrity In Pre-Surgical Planning, Nooshin Jafari Fesharaki
Resting-State Versus Breath-Hold For Testing Functional Magnetic Resonance Imaging Integrity In Pre-Surgical Planning, Nooshin Jafari Fesharaki
Theses and Dissertations
The neuro-vascular coupling mechanism responsible for blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) signals can be focally disrupted by various pathological factors (such as brain tumors) while leaving the underlying neurons functionally intact. Such neuro-vascular uncoupling (NVU) can pose serious complications for clinical use of fMRI. Mapping of cerebrovascular reactivity (CVR), which is a measure of the dilatory function of cerebral vasculature, can be a useful approach for detecting potential NVU. The widely-accepted approach for non-invasive CVR mapping requires the patient to perform a breath-hold challenge, which may have practical disadvantages for many patient populations. Thus, a …
Neural Substrates Of Fear Generalization And Its Associations With Anxiety And Intolerance Of Uncertainty, Ashley Ann Huggins
Neural Substrates Of Fear Generalization And Its Associations With Anxiety And Intolerance Of Uncertainty, Ashley Ann Huggins
Theses and Dissertations
Fear generalization - the tendency to interpret ambiguous stimuli as threatening due to perceptual similarity to a learned threat – is an adaptive process. Overgeneralization, however, is maladaptive and has been implicated in a number of anxiety disorders. Neuroimaging research has indicated several regions sensitive to effects of generalization, including regions involved in fear excitation (e.g., amygdala, insula) and inhibition (e.g., ventromedial prefrontal cortex). Research has suggested several other small brain regions may play an important role in this process (e.g., hippocampal subfields, bed nucleus of the stria terminalis [BNST], habenula), but, to date, these regions have not been examined …
Behavioral And Neural Correlates Of Episodic Memory Regulation, Mrinmayi Kulkarni
Behavioral And Neural Correlates Of Episodic Memory Regulation, Mrinmayi Kulkarni
Theses and Dissertations
Episodic memory retrieval, while critical for daily living, needs to be regulated to maintain goal-directed behavior. Past work has shown that episodic memory regulation engages brain regions involved in cognitive control, such as the dorsolateral and ventrolateral prefrontal cortex. These regions interact with the medial temporal lobe structures to control retrieval processes. In the current study, I paired eye-tracking, a sensitive index of memory, with fMRI in a novel paradigm to address several open questions in the field of episodic memory regulation. Participants initially encoded three celebrity faces and three tools with multiple indoor and outdoor scenes. In a subsequent …
Longitudinal Changes In Resting-State Functional Connectivity Of The Salience Network Among Individuals At-Risk For Ptsd Development, Kyrie Sellnow
Longitudinal Changes In Resting-State Functional Connectivity Of The Salience Network Among Individuals At-Risk For Ptsd Development, Kyrie Sellnow
Theses and Dissertations
Predicting post-traumatic stress disorder (PTSD) following a traumatic event has been a focus of recent neuroimaging research in the hopes of identifying key biomarkers that contribute to the disorder’s development. One possibility relies on understanding the connectivity between intrinsic connectivity networks (ICNs), including the salience network (SN). Prior research has consistently identified hyperconnectivity among SN regions among those with chronic PTSD, and this study aimed to examine the role of SN connectivity over time on PTSD symptom development. To do so, this study recruited individuals presenting to the Emergency Department with traumatic injuries to complete two resting-state fMRI scans: one …
Behavioral, Physiological, And Molecular Characterization Of Long-Term Administration Of A Novel Estrogen Receptor Beta Agonist In A Mouse Model Of Menopause, Aaron William Fleischer
Behavioral, Physiological, And Molecular Characterization Of Long-Term Administration Of A Novel Estrogen Receptor Beta Agonist In A Mouse Model Of Menopause, Aaron William Fleischer
Theses and Dissertations
The menopausal loss of circulating hormones, including estrogens, is associated with negative symptoms, such as hot flashes, anxiety and depression, cognitive decline, and weight gain. Although estrogenic hormone therapies (HT) prevent many of the negative symptoms related to the menopausal transition, these same therapies are associated with increased health risks, such as the development of breast and ovarian cancers, which is mediated by the activation of the a (ERa), but not b (ERb), estrogen receptor isoform. Furthermore, ERb agonism has previously been shown to reduce preclinical indices of hot flashes, memory decline, anxiety, and depression. As most ERb agonists are …
Functional Responding To Appetitive Faces Among Cannabis-Using Adolescents And Young Adults, Ryan Michael Sullivan
Functional Responding To Appetitive Faces Among Cannabis-Using Adolescents And Young Adults, Ryan Michael Sullivan
Theses and Dissertations
Cannabis use is associated with attenuated reward signaling, yet few studies have examined this relationship when viewing rewarding appetitive faces while undergoing functional neuroimaging. Furthermore, few neuroimaging analyses have examined the moderating role of gender on task-based fMRI outcomes. This study explored functional BOLD response elicited by appetitive faces while engaged in an affective go/no-go task, and specifically investigated the differences between cannabis-using and control groups, whether gender moderate findings, and brain-behavior associations. Participants (ages 16-26 years) were scanned after at least 3-weeks of monitored abstinence (cannabis-using group = 35; control group = 33). The findings demonstrated aberrant activation in …
Neural Correlates Underlying The Interactions Between Anxiety And Cannabis Use In Predicting Motor Response Inhibition, Richard Ward
Neural Correlates Underlying The Interactions Between Anxiety And Cannabis Use In Predicting Motor Response Inhibition, Richard Ward
Theses and Dissertations
The ability to effectively withhold an inappropriate response is a critical feature of cognitive control. Prior research indicates alterations in neural processes required for motor response inhibition in anxious individuals, including those with posttraumatic stress disorder (PTSD), and those who engage in regular cannabis use. However, thus far most research has examined how anxiety-related symptoms and cannabis use influence response inhibition in isolation of one another. The current study examined the interactions between anxious symptomology and recent cannabis use in a sample that recently experienced a traumatic event using functional magnetic resonance imaging (fMRI) during the completion of a Stop-Signal …
Sex- And Age-Associated Effects On The Retrosplenial Cortex Following Trace Fear Learning, Hanna Yousuf
Sex- And Age-Associated Effects On The Retrosplenial Cortex Following Trace Fear Learning, Hanna Yousuf
Theses and Dissertations
The rodent granular retrosplenial cortex (gRSC) forms reciprocal connections with the thalamus and hippocampus (Van Groen and Wyss, 1990, 1992; Sugar et al., 2011). The gRSC is well-positioned to coordinate information between higher-order brain structures to support complex forms of memory such as associative trace fear memories (Kwapis et al., 2014, 2015). Further, sex differences in fear learning and mechanisms underlying fear memories are observed in many of the brain regions implicated in trace fear learning such as the hippocampus, amygdala, and mPFC (Maren et al., 1994; Dalla et al., 2009; Gresack et al., 2009; Blume et al., 2017; Keiser …
Effects Of The Antidepressant Drug Vortioxetine On Ventral Pallidal Neuronal Activity, Respiration, And Heart Rate In The Rat, Piper Rogers
Effects Of The Antidepressant Drug Vortioxetine On Ventral Pallidal Neuronal Activity, Respiration, And Heart Rate In The Rat, Piper Rogers
Theses and Dissertations
Major Depressive Disorder (MDD) is a mental illness that affects millions of people worldwide. People diagnosed with MDD are often prescribed antidepressant drugs. Most antidepressants increase levels of serotonin (5-hydroxytryptamine, 5-HT) in the synapses between neurons. Selective-serotonin reuptake inhibitors (SSRIs), one class of antidepressants, do this by inhibiting the reuptake of serotonin released into the synapse. Serotonin neurons from the brainstem raphe nuclei affect a wide range of areas throughout the brain. Among these areas is the ventral pallidum (VP), located in the basal forebrain. Citalopram, an SSRI, has been found to increase the firing rate of action potentials of …
Physiological Consequences Of Neuromodulation And The Cellular Properties That Underlie Them, Margaret Louise Demaegd
Physiological Consequences Of Neuromodulation And The Cellular Properties That Underlie Them, Margaret Louise Demaegd
Theses and Dissertations
Neuronal activity is a product of more than the underlying neuronal connections. Modulatory influences like changes in the animal’s environment, the animals physiological state, or the release of neuromodulators can dramatically alter neuronal activity. Modulatory influences can be beneficial for the animal because they are a source of neuronal and behavioral plasticity, and they can provide neuronal circuits with the robustness needed to continue to function in new conditions, states, or tasks.However, malfunctions of the modulatory system can disrupt neuronal activity and lead to pathologies. Predicting how modulatory influences will alter neuronal activity is challenging because the underlying cellular and …
Alpha-Synuclein Multimerization Is Dependent On Structural Characteristics Of Repeated Ktkegv Regions, Benjamin Ira Rosen
Alpha-Synuclein Multimerization Is Dependent On Structural Characteristics Of Repeated Ktkegv Regions, Benjamin Ira Rosen
Theses and Dissertations
Parkinson’s disease (PD) is the most common movement disorder and is characterized by neuronal loss and the presence of Lewy bodies in dopaminergic neurons of the substantia nigra pars compacta. PD is a chronic, progressive, and irreversible neurodegenerative disorder associated with the selective loss of dopaminergic neurons. Initially described in an Ayurvedic medical treatise and Galen’s writings, and later by James Parkinson in 1817, the most common symptoms of PD are resting tremors, abnormal posture and gait, and muscle rigidity. Approximately 1 million people are living with PD in the United States and worldwide estimates are between 7 and 10 …
Microrna Regulation And Cellular Proteostasis In Parkinson's Disease, Alberim Kurtishi
Microrna Regulation And Cellular Proteostasis In Parkinson's Disease, Alberim Kurtishi
Theses and Dissertations
Parkinson’s disease (PD) is a chronic and progressive neurodegenerative disorder predominately affecting the aging population. It is the second most common neurodegenerative disorder after Alzheimer’s disease (AD) affecting over 1 million individuals in the US alone. Recent studies have tried to understand the exact nature in which healthy neurons transition to a degenerative state in PD. There are a multitude of combinatory factors that can lead to the development of PD including environmental factors, genetic factors, and aging. The majority of PD cases are sporadic in nature, however familial cases account for 5-10% of total PD cases world-wide. The hallmark …
Rna Splicing In Neuron Physiology And Neurodegenerative Diseases, Md Faruk Hossain
Rna Splicing In Neuron Physiology And Neurodegenerative Diseases, Md Faruk Hossain
Theses and Dissertations
Gene expression is regulated at multiple levels, including transcription, RNA editing, pre-mRNA splicing, mRNA export, translation, and posttranslational modifications. Alternative splicing is a process by which exons can be included or excluded, giving rise to multiple mRNA isoforms from the same transcript. Alternative splicing is an important mechanism in developmental, tissue- and cell-specific control of gene expression, and it is key for expanding proteomic diversity and complexity from a limited number of genes. Moreover, more than 95% of multiexon genes undergo alternative splicing in humans, and about half of all disease-causing point mutations in humans affect pre-mRNA splicing, including neurological …
Evaluating Neuromuscular Function Of The Biceps Brachii After Spinal Cord Injury: Assessment Of Voluntary Activation And Motor Evoked Potential Input-Output Curves Using Transcranial Magnetic Stimulation, Thibault Roumengous
Theses and Dissertations
Activation of upper limb muscles is important for independent living after cervical spinal cord injury (SCI) that results in tetraplegia. An emerging, non-invasive approach to address post-SCI muscle weakness is modulation of the nervous system. A long-term goal is to develop neuromodulation techniques to reinnervate (i.e. resupply nerve to) muscle fiber and thereby increase muscle function in individuals with tetraplegia. Towards this goal, developing monitoring techniques to quantify neuromuscular function is needed to better direct neurorehabilitation. Assessment of voluntary activation (VA) is a promising approach because the location of the stimulus can be applied cortically using transcranial magnetic stimulation (TMS) …
Investigating Cannabinoid Type-1 Receptor (Cb1r) Positive Allosteric Modulators (Pams) In Mouse Models Of Overt Cannabimimetic Activity, Subjective Drug Effects, And Neuropathic Pain, Jayden Elmer
Theses and Dissertations
Chronic pain affects between 20 and 30 percent of the adult population in western countries and represents a wide array of specific etiologies (Berge, 2011). Neuropathic pain secondary to traumatic nerve injury, chemotherapeutic toxicity, or diseases (e.g., diabetes mellitus) is often refractory to conventional analgesics, with patients receiving less than 50% pain relief compared to placebo (Finnerup et al. 2010). The endocannabinoid system has shown potential as a therapeutic target for neuropathic pain wherein CB1 agonism via administration of exogenous agonists or pharmacological blockade of endocannabinoid catabolic enzymes exhibits efficacy in reversing allodynia in the chronic constriction injury (CCI) model …
Muscarinic Excitation Of Dopamine Neurons In The Ventral Tegmental Area Via Activation Of A Trpc-Like Cation Conductance, Yu Tzu Chen
Theses and Dissertations
Dopaminergic (DA) neurons in the ventral tegmental area (VTA) play a crucial role in reward and motivational behaviors, including the development of drug addictions. VTA DA neurons receive excitatory cholinergic inputs from the mesopontine tegmentum. Blockage of the M5 muscarinic receptor in DA neurons has been shown to attenuate drug-induced DA release and abuse-related behaviors, but the molecular mechanism is unknown. In this study, experiments were designed to identify the electrophysiological effects of muscarinic agonism in the modulation of action potential kinetics and firing patterns in VTA DA neurons of mice. Pharmacology of the muscarinic receptor-evoked current was also characterized. …
Interclass Gpcr Heteromerization Affects Localization And Trafficking, Rudy Toneatti
Interclass Gpcr Heteromerization Affects Localization And Trafficking, Rudy Toneatti
Theses and Dissertations
Class A serotonin (5-hydroxytryptamine) 2A (5-HT2AR) and class C metabotropic glutamate 2 receptors (mGluR2) are seven transmembrane receptors (7TMRs or G protein-coupled receptors – GPCRs) involved in multiple neuropsychiatric disorders including schizophrenia. Previous findings from our laboratory reported that 5-HT2AR and mGluR2 are dysregulated in the prefrontal cortex of patients suffering from this psychiatric condition, although 5-HT2AR’s expression was recovered in antipsychotic-medicated patients. Genome-wide association studies on schizophrenia reported that endosomal trafficking that regulates cell surface abundance of another 7TMR implicated in this disease (dopamine D2 receptor) can be altered. Ligand-activated receptors, including the …
Glucocorticoid Receptor Dysregulation Underlies 5-Ht2a Receptor-Dependent Synaptic And Behavioral Deficits In A Mouse Neurodevelopmental Disorder Model, Justin M. Saunders
Glucocorticoid Receptor Dysregulation Underlies 5-Ht2a Receptor-Dependent Synaptic And Behavioral Deficits In A Mouse Neurodevelopmental Disorder Model, Justin M. Saunders
Theses and Dissertations
Schizophrenia is a severe neuropsychiatric disorder that presents with diverse symptoms, some of which remain resistant to treatment. Increased risk of neurodevelopmental disorders such as schizophrenia has been observed following gestational infection in humans, leading to development of maternal immune activation (MIA) animal models. Increased density of the serotonin 5-HT2AR receptor (5-HT2AR), the primary target of hallucinogenic drugs and a key target of atypical antipsychotics, has been observed in postmortem antipsychotic-free prefrontal cortex samples from schizophrenia subjects, a change reflected in frontal cortex of adult MIA offspring. To model MIA, we administered 20 mg/kg i.p. of the viral mimetic poly-(I:C) …