Physiology Commons^™

Activation Of Renal Epithelial Na+ Channels (Enac) In Infants With Congenital Heart Disease, Laura Ortmann, Shyam Sundar Nandi, Yulong Li, Hong Zheng, Kaushik K. Patel

Journal Articles: Cellular & Integrative Physiology

INTRODUCTION: This study was designed to measure the concentration and activity of urinary proteases that activate renal epithelial sodium channel (ENaC) mediated Na

METHODS: Urine samples from infants undergoing cardiac surgery were collected at three time points: T1) pre-operatively, T2) 6-8 h after surgery, and T3) 24 h after diuretics. Urine was collected from five heathy infant controls. The urine was tested for four proteases and whole-cell patch-clamp testing was conducted in renal collecting duct M-1 cells to test whether patient urine increased Na

RESULTS: Heavy chain of plasminogen, furin, and prostasin were significantly higher in cardiac patients prior to …

Innate And Adaptive Immune System Consequences Of Post-Traumatic Stress Disorder, Tatlock H. Lauten, Tamara Natour, Adam J. Case

Journal Articles: Cellular & Integrative Physiology

In the field of psychiatry, biological markers are rarely, if ever, used in the diagnosis of mental health disorders. Clinicians rely primarily on patient histories and behavioral symptoms to identify specific psychopathologies, which makes diagnosis highly subjective. Moreover, therapies for mental health disorders are aimed specifically at attenuating behavioral manifestations, which overlooks the pathophysiological indices of the disease. This is highly evident in posttraumatic stress disorder (PTSD) where inflammation and immune system perturbations are becoming increasingly described. Further, patients with PTSD possess significantly elevated risks of developing comorbid inflammatory diseases such as autoimmune and cardiovascular diseases, which are likely linked …

Invited Review: Adrenocortical Function In Avian And Non-Avian Reptiles: Insights From Dispersed Adrenocortical Cells., Rocco V. Carsia, Patrick J. Mcilroy, Henry B John-Alder

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Herein we review our work involving dispersed adrenocortical cells from several lizard species: the Eastern Fence Lizard (Sceloporus undulatus), Yarrow's Spiny Lizard (Sceloporus jarrovii), Striped Plateau Lizard (Sceloporus virgatus) and the Yucatán Banded Gecko (Coleonyx elegans). Early work demonstrated changes in steroidogenic function of adrenocortical cells derived from adult S. undulatus associated with seasonal interactions with sex. However, new information suggests that both sexes operate within the same steroidogenic budget over season. The observed sex effect was further explored in orchiectomized and ovariectomized lizards, some supported with exogenous testosterone. Overall, a suppressive effect of testosterone was evident, especially in cells …

Restoration Of Normal Blood Flow In Atherosclerotic Arteries Promotes Plaque Stabilization, Morgan A. Schake, Ian S. Mccue, Evan T. Curtis, Thomas J. Ripperda, Samuel Harvey, Bryan T. Hackfort, Anna Fitzwater, Yiannis S. Chatzizisis, Forrest M. Kievit, Ryan M. Pedrigi

Journal Articles: Cellular & Integrative Physiology

Blood flow is a key regulator of atherosclerosis. Disturbed blood flow promotes atherosclerotic plaque development, whereas normal blood flow protects against plaque development. We hypothesized that normal blood flow is also therapeutic, if it were able to be restored within atherosclerotic arteries. Apolipoprotein E-deficient (ApoE^−/−) mice were initially instrumented with a blood flow-modifying cuff to induce plaque development and then five weeks later the cuff was removed to allow restoration of normal blood flow. Plaques in decuffed mice exhibited compositional changes that indicated increased stability compared to plaques in mice with the cuff maintained. The therapeutic benefit of …

Repeated Social Defeat Stress Leads To Immunometabolic Shifts In Innate Immune Cells Of The Spleen, Mandakh Bekhbat, John Drake, Emily C. Reed, Tatlock H. Lauten, Tamara Natour, Vladimir I. Vladimirov, Adam J. Case

Journal Articles: Cellular & Integrative Physiology

Psychosocial stress has been shown to prime peripheral innate immune cells, which take on hyper-inflammatory phenotypes and are implicated in depressive-like behavior in mouse models. However, the impact of stress on cellular metabolic states that are thought to fuel inflammatory phenotypes in immune cells are unknown. Using single cell RNA-sequencing, we investigated mRNA enrichment of immunometabolic pathways in innate immune cells of the spleen in mice subjected to repeated social defeat stress (RSDS) or no stress (NS). RSDS mice displayed a significant increase in the number of splenic macrophages and granulocytes (p < 0.05) compared to NS littermates. RSDS-upregulated genes in macrophages, monocytes, and granulocytes significantly enriched immunometabolic pathways thought to play a role in myeloid-driven inflammation (glycolysis, HIF-1 signaling, MTORC1 signaling) as well as pathways related to oxidative phosphorylation (OXPHOS) and oxidative stress (p < 0.05 and FDR<0.1). These results suggest that the metabolic enhancement reflected by upregulation of glycolytic and OXPHOS pathways may be important for cellular proliferation of splenic macrophages and granulocytes following repeated stress exposure. A better understanding of these intracellular metabolic mechanisms may ultimately help develop novel strategies to reverse the impact of stress and associated peripheral immune changes on the brain and behavior.

Defining The Nuanced Nature Of Redox Biology In Post-Traumatic Stress Disorder, Emily C. Reed, Adam J. Case

Journal Articles: Cellular & Integrative Physiology

Post-traumatic stress disorder (PTSD) is a mental health disorder that arises after experiencing or witnessing a traumatic event. Despite affecting around 7% of the population, there are currently no definitive biological signatures or biomarkers used in the diagnosis of PTSD. Thus, the search for clinically relevant and reproducible biomarkers has been a major focus of the field. With significant advances of large-scale multi-omic studies that include genomic, proteomic, and metabolomic data, promising findings have been made, but the field still has fallen short. Amongst the possible biomarkers examined, one area is often overlooked, understudied, or inappropriately investigated: the field of …

Enhanced Central Sympathetic Tone Induces Heart Failure With Preserved Ejection Fraction (Hfpef) In Rats, Shyam S. Nandi, Kenichi Katsurada, Michael J. Moulton, Hong Zheng, Kaushik K. Patel

Journal Articles: Cellular & Integrative Physiology

Heart failure with preserved ejection fraction (HFpEF) is a heterogenous clinical syndrome characterized by diastolic dysfunction, concentric cardiac left ventricular (LV) hypertrophy, and myocardial fibrosis with preserved systolic function. However, the underlying mechanisms of HFpEF are not clear. We hypothesize that an enhanced central sympathetic drive is sufficient to induce LV dysfunction and HFpEF in rats. Male Sprague-Dawley rats were subjected to central infusion of either saline controls (saline) or angiotensin II (Ang II, 20 ng/min, i.c.v) via osmotic mini-pumps for 14 days to elicit enhanced sympathetic drive. Echocardiography and invasive cardiac catheterization were used to measure systolic and diastolic …

Repeated Social Defeat Stress Induces An Inflammatory Gut Milieu By Altering The Mucosal Barrier Integrity And Gut Microbiota Homeostasis, Santosh K. Yadav, Rizwan Ahmad, Cassandra M. Moshfegh, Jagadesan Sankarasubramanian, Vineet A. Joshi, Safwan K. Elkhatib, Yashpal S. Chhonker, Goeffrey A. Talmon, Chittibabu Guda, Adam Case, Amar B. Singh

Journal Articles: Cellular & Integrative Physiology

Background

Posttraumatic stress disorder (PTSD) is a mental health condition triggered by exposure to traumatic events in an individual’s life. Patients with PTSD are also at a higher risk for comorbidities. However, it is not well understood how PTSD affects human health and/or promotes the risk for comorbidities. Nevertheless, patients with PTSD harbor a proinflammatory milieu and dysbiotic gut microbiota. Gut barrier integrity helps to maintain normal gut homeostasis and its dysregulation promotes gut dysbiosis and inflammation.

Methods

We used a mouse model of repeated social defeat stress (RSDS), a preclinical model of PTSD. Behavioral studies, metagenomics analysis of the …

A Critical Role For Staphylococcal Nitric Oxide Synthase In Controlling Flavohemoglobin Toxicity, Ryan M. Singh, Sujata S. Chaudhari, Sasmita Panda, Elizabeth H. Hutfless, Cortney E. Heim, Dhananjay Shinde, Abdulelah A. Alqarzaee, Margaret F. Sladek, Vineet Kumar, Matthew C. Zimmerman, Paul D. Fey, Tammy Kielian, Vinai Chittezham Thomas

Journal Articles: Cellular & Integrative Physiology

Most coagulase-negative staphylococcal species, including the opportunistic pathogen Staphylococcus epidermidis, struggle to maintain redox homeostasis and grow under nitrosative stress. Under these conditions, growth can only resume once nitric oxide (NO) is detoxified by the flavohemoglobin Hmp. Paradoxically, S. epidermidis produces endogenous NO through its genetically encoded nitric oxide synthase (seNOS) and heavily relies on its activity for growth. In this study, we investigate the basis of the growth advantage attributed to seNOS activity. Our findings reveal that seNOS supports growth by countering Hmp toxicity. S. epidermidis relies on Hmp activity for its survival in the host under NO stress. …

Potential Of Synthetic And Natural Compounds As Novel Histone Deacetylase Inhibitors For The Treatment Of Hematological Malignancies, Dilipkumar Pal, Khushboo Raj, Shyam Sundar Nandi, Surajit Sinha, Abhishek Mishra, Arijit Mondal, Ricardo Lagoa, Jack T. Burcher, Anupam Bishayee

Journal Articles: Cellular & Integrative Physiology

Histone deacetylases (HDACs) and histone acetyltransferases (HATs) are enzymes that remove or add acetyl groups to lysine residues of histones, respectively. Histone deacetylation causes DNA to more snugly encircle histones and decreases gene expression, whereas acetylation has the opposite effect. Through these small alterations in chemical structure, HATs and HDACs regulate DNA expression. Recent research indicates histone deacetylase inhibitors (HDACis) may be used to treat malignancies, including leukemia, B-cell lymphoma, virus-associated tumors, and multiple myeloma. These data suggest that HDACis may boost the production of immune-related molecules, resulting in the growth of CD8-positive T-cells and the recognition of nonreactive tumor …

Elevated Crp And Tnf-Α Levels Are Associated With Blunted Neural Oscillations Serving Fluid Intelligence, Sarah M. Dietz, Mikki Schantell, Rachel K. Spooner, Megan E. Sandal, Amirsalar Mansouri, Yasra Arif, Hannah J. Okelberry, Jason A. John, Ryan Glesinger, Pamela E. May, Elizabeth Heinrichs-Graham, Adam J. Case, Matthew C. Zimmerman, Tony W. Wilson

Journal Articles: Cellular & Integrative Physiology

INTRODUCTION: Inflammatory processes help protect the body from potential threats such as bacterial or viral invasions. However, when such inflammatory processes become chronically engaged, synaptic impairments and neuronal cell death may occur. In particular, persistently high levels of C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α) have been linked to deficits in cognition and several psychiatric disorders. Higher-order cognitive processes such as fluid intelligence (Gf) are thought to be particularly vulnerable to persistent inflammation. Herein, we investigated the relationship between elevated CRP and TNF-α and the neural oscillatory dynamics serving Gf.

METHODS: Seventy adults between the ages of 20-66 years …

Commonalities And Differences In Carotid Body Dysfunction In Hypertension And Heart Failure, Igor S. A. Felippe, Rodrigo Del Río, Harold D. Schultz, Benedito H. Machado, Julian F R Paton

Journal Articles: Cellular & Integrative Physiology

Carotid body pathophysiology is associated with many cardiovascular-respiratory-metabolic diseases. This pathophysiology reflects both hyper-sensitivity and hyper-tonicity. From both animal models and human patients, evidence indicates that amelioration of this pathophysiological signalling improves disease states such as a lowering of blood pressure in hypertension, a reduction of breathing disturbances with improved cardiac function in heart failure (HF) and a re-balancing of autonomic activity with lowered sympathetic discharge. Given this, we have reviewed the mechanisms of carotid body hyper-sensitivity and hyper-tonicity across disease models asking whether there is uniqueness related to specific disease states. Our analysis indicates some commonalities and some potential …

Observing Ceramide Pathway With Ferroptosis Via Mia Paca-2 Cell Treatment With Rsl3, Tazrin Rahman

Auctus: The Journal of Undergraduate Research and Creative Scholarship

Composed of sphingosine and a fatty acid, ceramides are lipid molecules that serve as key metabolic signaling molecules of a sphingolipid pathway. While it acts as a precursor of complex sphingolipids, inducing ceramide generation can cause cell stress leading to subsequent cell death via apoptosis, necrosis, and even mitophagy. With regards to cell death specifically, a novel form of regulated cell death, ferroptosis, has recently been recognized of necrotic nature. Its unique morphological features and distinct properties have been observed over the last several decades; however, the molecular features were not identifiable as pure evidence of cell death, until recently …

Evaluating College Students’ Health Literacy And Its Effects On Their Perceptions Of Information Concerning Mask-Wearing In The Covid-19 Pandemic Ve Information Concerning Mask-Wearing In The Covid-19 Pandemic, Hannah S. Ketchum

Honors Program Projects

Background: Mask-wearing was a controversial and polarizing phenomenon during the COVID-19 pandemic. Beliefs concerning mask-wearing differed depending on sources of information concerning the pandemic, levels of health literacy, political leaning, demographics, or other factors. This project attempted to connect college students’ level of health literacy to their understanding of and adherence to mask-wearing in the COVID-19 pandemic. There is a gap in research connecting health literacy to understanding information concerning pandemics and an even bigger lack of studies conducted that relate college students’ health literacy to their perception of illnesses or pandemics. It is important to understand the impact of …

Cellular Bioenergetics: Experimental Evidence For Alcohol-Induced Adaptations, Liz Simon, Patricia E. Molina

School of Medicine Faculty Publications

At-risk alcohol use is associated with multisystemic effects and end-organ injury, and significantly contributes to global health burden. Several alcohol-mediated mechanisms have been identified, with bioenergetic maladaptation gaining credence as an underlying pathophysiological mechanism contributing to cellular injury. This evidence-based review focuses on the current knowledge of alcohol-induced bioenergetic adaptations in metabolically active tissues: liver, cardiac and skeletal muscle, pancreas, and brain. Alcohol metabolism itself significantly interferes with bioenergetic pathways in tissues, particularly the liver. Alcohol decreases states of respiration in the electron transport chain, and activity and expression of respiratory complexes, with a net effect to decrease ATP content. …

Women's Health: Optimal Nutrition Throughout The Lifecycle, Edith J M Feskens, Regan Bailey, Zulfiqar Ahmed Bhutta, Hans-Konrad Biesalski, Heather Eicher-Miller, Klaus Krämer, Wen-Harn Pan, James C. Griffiths

Department of Paediatrics and Child Health

Sex differences are an important consideration when researching and establishing policies for nutrition and optimal health. For women's health, there are important physiologic, neurologic, and hormonal distinctions throughout the lifecycle that impact nutritional needs. Distinct from those for men, these nutritional needs must be translated into appropriate nutrition policy that aims to not only avoid overt nutritional deficiency, but also to promote health and minimize risk for chronic disease. Through a series of webinars, scientific experts discussed the advances in the understanding of the unique nutritional needs, challenges and opportunities of the various life stages for women across the life …

Investigation Of Oncogenic Ras And Endoplasmic Reticulum-Mitochondria Calcium Flux And Their Relationship In The Context Of Tumorigenesis, Emma Anderson

Senior Honors Theses

Intracellular calcium as a signaling molecule is a pervasive feature of cellular pathways, especially those that manage internal homeostasis and transitions through the cell cycle, so much so that regulated, responsive calcium flux between the endoplasmic reticulum (ER) and the mitochondria has been suggested to play a major role in cancer development. Another factor commonly implicated in tumorigenesis is RAS, an oncogene that controls signaling for many pathways that are also regulated by calcium. While both calcium and oncogenic RAS signaling are implicated in cancer development, possible links between them have yet to be determined. The identification of these links …

Gut Microbiome And Metabolome Variations In Self-Identified Muscle Builders Who Report Using Protein Supplements, Lauri O. Byerley, Karyn M. Gallivan, Courtney J. Christopher, Christopher M. Taylor, Meng Luo, Scot E. Dowd, Gregory M. Davis, Hector F. Castro, Shawn R. Campagna, Kristin S. Ondrak

School of Graduate Studies Faculty Publications

Muscle builders frequently consume protein supplements, but little is known about their effect on the gut microbiota. This study compared the gut microbiome and metabolome of selfidentified muscle builders who did or did not report consuming a protein supplement. Twenty-two participants (14 males and 8 females) consumed a protein supplement (PS), and seventeen participants (12 males and 5 females) did not (No PS). Participants provided a fecal sample and completed a 24-h food recall (ASA24). The PS group consumed significantly more protein (118 ± 12 g No PS vs. 169 ± 18 g PS, p = 0.02). Fecal metabolome and …

Time-Dependent Alteration In The Chemoreflex Post-Acute Lung Injury, Kajal Kamra, Nikolay Karpuk, Ryan Adam, Irving H. Zucker, Harold D. Schultz, Han-Jun Wang

Journal Articles: Cellular & Integrative Physiology

Acute lung injury (ALI) induces inflammation that disrupts the normal alveolar-capillary endothelial barrier which impairs gas exchange to induce hypoxemia that reflexively increases respiration. The neural mechanisms underlying the respiratory dysfunction during ALI are not fully understood. The purpose of this study was to investigate the role of the chemoreflex in mediating abnormal ventilation during acute (early) and recovery (late) stages of ALI. We hypothesized that the increase in respiratory rate (fR) during post-ALI is mediated by a sensitized chemoreflex. ALI was induced in male Sprague-Dawley rats using a single intra-tracheal injection of bleomycin (Bleo: low-dose = 1.25 mg/Kg or …

Comparative Genomics, Evolutionary Epidemiology, And Rbd-Hace2 Receptor Binding Pattern In B.1.1.7 (Alpha) And B.1.617.2 (Delta) Related To Their Pandemic Response In Uk And India, Chiranjib Chakraborty, Ashish Ranjan Sharma, Manojit Bhattacharya, Bidyut Mallik, Shyam Sundar Nandi, Sang-Soo Lee

Journal Articles: Cellular & Integrative Physiology

BACKGROUND: The massive increase in COVID-19 infection had generated a second wave in India during May-June 2021 with a critical pandemic situation. The Delta variant (B.1.617.2) was a significant factor during the second wave. Conversely, the UK had passed through the crucial phase of the pandemic from November to December 2020 due to B.1.1.7. The study tried to comprehend the pandemic response in the UK and India to the spread of the B.1.1.7 (Alpha, UK) variant and B.1.617.2 (Delta, India) variant.

METHODS: This study was performed in three directions to understand the pandemic response of the two emerging variants. First, …

T-Lymphocyte Tyrosine Hydroxylase Regulates T H 17 T-Lymphocytes During Repeated Social Defeat Stress, Safwan K. Elkhatib, Cassandra M. Moshfegh, Gabrielle F. Watson, Adam J. Case

Journal Articles: Cellular & Integrative Physiology

Posttraumatic stress disorder (PTSD) is a debilitating psychiatric disorder which results in deleterious changes to psychological and physical health. Patients with PTSD are especially susceptible to life-threatening co-morbid inflammation-driven pathologies, such as autoimmunity, while also demonstrating increased T-helper 17 (T_H17) lymphocyte-driven inflammation. While the exact mechanism of this increased inflammation is unknown, overactivity of the sympathetic nervous system is a hallmark of PTSD. Neurotransmitters of the sympathetic nervous system (i.e., catecholamines) can alter T-lymphocyte function, which we have previously demonstrated to be partially mitochondrial redox-mediated. Furthermore, we have previously elucidated that T-lymphocytes generate their own catecholamines, and strong …

Inhibition Of Bruton Tyrosine Kinase Reduces Neuroimmune Cascade And Promotes Recovery After Spinal Cord Injury, Chen Guang Yu, Vimala Bondada, Hina Iqbal, Kate L. Moore, John C. Gensel, Subbarao Bondada, James W. Geddes

Physiology Faculty Publications

Microglia/astrocyte and B cell neuroimmune responses are major contributors to the neurological deficits after traumatic spinal cord injury (SCI). Bruton tyrosine kinase (BTK) activation mechanistically links these neuroimmune mechanisms. Our objective is to use Ibrutinib, an FDA-approved BTK inhibitor, to inhibit the neuroimmune cascade thereby improving locomotor recovery after SCI. Rat models of contusive SCI, Western blot, immunofluorescence staining imaging, flow cytometry analysis, histological staining, and behavioral assessment were used to evaluate BTK activity, neuroimmune cascades, and functional outcomes. Both BTK expression and phosphorylation were increased at the lesion site at 2, 7, 14, and 28 days after SCI. Ibrutinib …

Ketone Body Metabolism In The Ischemic Heart, Stephen C. Kolwicz Jr.

Health and Exercise Physiology Faculty Publications

Ketone bodies have been identified as an important, alternative fuel source in heart failure. In addition, the use of ketone bodies as a fuel source has been suggested to be a potential ergogenic aid for endurance exercise performance. These findings have certainly renewed interest in the use of ketogenic diets and exogenous supplementation in an effort to improve overall health and disease. However, given the prevalence of ischemic heart disease and myocardial infarctions, these strategies may not be ideal for individuals with coronary artery disease. Although research studies have clearly defined changes in fatty acid and glucose metabolism during ischemia …

Race And Drug Toxicity: A Study Of Three Cardiovascular Drugs With Strong Pharmacogenetic Recommendations., Travis J. O'Brien, Kevin Fenton, Alfateh Sidahmed, April Barbour, Arthur F Harralson

Pharmacology and Physiology Faculty Publications

No abstract provided.

Fibroblast Growth Factor 19 Increases The Excitability Of Pre-Motor Glutamatergic Dorsal Vagal Complex Neurons From Hyperglycemic Mice, Jordan B. Wean, Bret N. Smith

Physiology Faculty Publications

Intracerebroventricular administration of the protein hormone fibroblast growth factor 19 (FGF19) to the hindbrain produces potent antidiabetic effects in hyperglycemic mice that are likely mediated through a vagal parasympathetic mechanism. FGF19 increases the synaptic excitability of parasympathetic motor neurons in the dorsal motor nucleus of the vagus (DMV) from hyperglycemic, but not normoglycemic, mice but the source of this synaptic input is unknown. Neurons in the area postrema (AP) and nucleus tractus solitarius (NTS) express high levels of FGF receptors and exert glutamatergic control over the DMV. This study tested the hypothesis that FGF19 increases glutamate release in the DMV …

Editorial: Recent Advances In Cardiotoxicity Testing, Tamer M. A. Mohamed, Javid Moslehi, Jonathan Satin

Physiology Faculty Publications

No abstract provided.

Editorial: The Metabolism Of The Neuron-Glia Unit, Yannick Poitelon, Lance A. Johnson, Marie-Ève Tremblay

Physiology Faculty Publications

No abstract provided.

Apoε4 Lowers Energy Expenditure In Females And Impairs Glucose Oxidation By Increasing Flux Through Aerobic Glycolysis, Brandon C. Farmer, Holden C. Williams, Nicholas A. Devanney, Margaret A. Piron, Grant K. Nation, David J. Carter, Adeline E. Walsh, Rebika Khanal, Lyndsay E. A. Young, Jude C. Kluemper, Gabriela Hernandez, Elizabeth J. Allenger, Rachel Mooney, Lesley R. Golden, Cathryn T. Smith, J. Anthony Brandon, Vedant A. Gupta, Philip A. Kern, Matthew S. Gentry, Josh M. Morganti, Ramon C. Sun, Lance A. Johnson

Physiology Faculty Publications

BACKGROUND: Cerebral glucose hypometabolism is consistently observed in individuals with Alzheimer's disease (AD), as well as in young cognitively normal carriers of the Ε4 allele of Apolipoprotein E (APOE), the strongest genetic predictor of late-onset AD. While this clinical feature has been described for over two decades, the mechanism underlying these changes in cerebral glucose metabolism remains a critical knowledge gap in the field.

METHODS: Here, we undertook a multi-omic approach by combining single-cell RNA sequencing (scRNAseq) and stable isotope resolved metabolomics (SIRM) to define a metabolic rewiring across astrocytes, brain tissue, mice, and human subjects expressing APOE4.

RESULTS: Single-cell …

Reduced Mitochondrial Dna And Oxphos Protein Content In Skeletal Muscle Of Children With Cerebral Palsy, Ferdinand Von Walden, Ivan J. Vechetti Jr., Davis A. Englund, Vandré C. Figueiredo, Rodrigo Fernandez-Gonzalo, Kevin A. Murach, Jessica Pingel, John J. Mccarthy, Per Stål, Eva Pontén

Physiology Faculty Publications

AIM: To provide a detailed gene and protein expression analysis related to mitochondrial biogenesis and assess mitochondrial content in skeletal muscle of children with cerebral palsy (CP).

METHOD: Biceps brachii muscle samples were collected from 19 children with CP (mean [SD] age 15y 4mo [2y 6mo], range 9-18y, 16 males, three females) and 10 typically developing comparison children (mean [SD] age 15y [4y], range 7-21y, eight males, two females). Gene expression (quantitative reverse transcription polymerase chain reaction [PCR]), mitochondrial DNA (mtDNA) to genomic DNA ratio (quantitative PCR), and protein abundance (western blotting) were analyzed. Microarray data sets (CP/aging/bed rest) were …

Synphilin-1 And Its Effects On Pathogenesis Of Parkinson’S Disease, Mirghani Mohamed

Honors Scholar Theses

Parkinson's Disease (PD) is a progressive neurodegenerative and movement disorder primarily caused by the degradation of dopaminergic neurons. Known markers of neurodegeneration in PD are Lewy Bodies, which are fibrillar aggregates that are found in the brains of PD patients. Lewy Bodies can accumulate from specific mutations in the SNCA gene that codes for alpha-synuclein, a protein enriched in presynaptic neurons. A mutated SNCA gene can cause conformational aggregates of alpha-synuclein to form toxic species mediating neuronal death. Research into alpha-synuclein has led to the discovery of a binding partner known as synphilin-1 that is also found in protein aggregates …