Life Sciences Commons^™

Psychological Trauma Alters T-Lymphocyte Inflammation And Redox Through Sympathetic Mechanisms, Safwan K. Elkhatib

Theses & Dissertations

Posttraumatic stress disorder (PTSD) is a devastating psychiatric disorder characterized by distinctive symptom clusters, including intrusive memories (i.e., flashbacks), avoidance of related stimuli, affective changes, and hyperarousal. Strikingly, patients with PTSD face a significantly increased risk for a number of inflammation-driven pathologies, ranging from cardiovascular to autoimmune disease. Yet, the exact etiology of this increased risk remains unknown. The immune system is known to be strongly influenced by the sympathetic nervous system, and sympathetic overactivity is a hallmark of PTSD. Lymphoid organs, such as the spleen, are richly innervated by sympathetic nerve fibers which terminate near adaptive immune …

The Role Of Central Ace2 And Nrf2 In Sympatho-Excitation: Responses To Central Angiotensin Ii, Anyun Ma

Theses & Dissertations

Sympatho-excitation is a key characteristic in cardiovascular diseases such as chronic heart failure (CHF) and primary Hypertension (HTN). Evidence suggests that increased sympathetic tone is closely related to activation of the Renin-Angiotensin-Aldosterone system (RAAS) in the central nervous system. An underlying mechanism for sympatho-excitation is thought to be oxidative stress resulting from Angiotensin II (AngII) type 1 receptor (AT1R) activation. Over the past several decades, pharmacological targeting of components of the RAAS have been used as standard therapy in CHF and HTN. However, additional therapeutic strategies are necessary to control these diseases. Oxidative stress is regulated, in part, by the …

Role Of Eps15 Homology Domain-Containing Protein 4 (Ehd4) In The Kidney, Shamma Rahman

Theses & Dissertations

In the kidney, endocytic recycling regulates the abundance of channels and transporters in the membrane of the tubular epithelium, and thereby controls the kidney’s ability to regulate water homeostasis. In recent years, a family of proteins called Eps15 homology domain-containing (EHD) proteins has emerged as important regulators of the endocytic recycling pathway. Mammals express four paralogs of EHD proteins, EHD1-4, that are expressed in different tissues. Although EHD4 is expressed in the kidney, the specific physiological role of EHD4 in the kidney remains unknown. Therefore, this dissertation was focused to elucidate the physiological role of EHD4 in the kidney. In …

Target Validation And Pharmacological Characterization Of Novel Nmdar Modulators, Kiran Sapkota

Theses & Dissertations

The N-methyl-D aspartate receptors (NMDARs) are ligand-gated ion channels, which play important roles in learning and memory. Excessive activity of NMDARs is implicated in damage due to stroke and neurodegenerative diseases, whereas hypoactivity of NMDARs contributes to schizophrenia. The initial goal of my dissertation is to evaluate the potential role of the GluN2D-containing NMDARs in neuropathological, behavioral and cognitive alterations associated with schizophrenia and characterize the pharmacology and mechanisms of action of NMDAR modulators which could potentially be used to modulate these receptors in schizophrenia.

A subanesthetic dose of the NMDAR antagonist ketamine elicits symptoms of schizophrenia. This property led …

Molecular Mechanisms Of Necrotic Cell Death In Ischemic Renal Injury, Yuan Ying

Theses & Dissertations

Acute kidney injury is a common clinical syndrome particularly in hospitalized patients. Necrotic cell death, as one type of major cell death after ischemic reperfusion injury, is partially responsible for the rapid decline in GFR. p53 is a novel apoptosis and necrosis inducer and is found to be activated after ischemic renal injury. Although previous studies suggest that p53 could be an important mediator of kidney dysfunction, no studies have examined its role in necrotic cell death and the cross talk between p53 and other necrotic cell inducers such as PARP-1 and CypD. Thus, in this study our first goal …

Interaction Between Angiotensin Ii And Bdnf In Modulating Sympathetic Nerve Activity, Bryan K. Becker

Theses & Dissertations

Over activation of the sympathetic nervous system is prevalent in many forms of cardiovascular disease such as chronic heart failure (CHF) and hypertension. Although increased neuronal renin-angiotensin system activity in presympathetic neurons has been well implicated in mediating this sympatho-excitation, many of the neuronal effects of angiotensin II (Ang II) signaling remain poorly understood. One particular mechanism of Ang II-mediated increases in presympathetic neuronal activity is through reductions in voltage-gated K⁺ currents. Another pathway that has profound effects on neuronal K⁺ currents and that has been previously implicated in Ang II-signaling is brain-derived neurotrophic factor (BDNF) activity through …