Medical Sciences Commons^™

Ethanol And Opioids Do Not Act Synergistically To Depress Excitation In Carotid Body Type I Cells, Ryan J. Rakoczy, Kajal Kamra, Yoon-Jae Yi, Christopher N. Wyatt

Neuroscience, Cell Biology & Physiology Faculty Publications

The combination of opioids and ethanol can synergistically depress breathing and the acute ventilatory response to hypoxia. Multiple studies have shown that the underlying mechanisms for this may involve calcium channel inhibition in central neurons. But we have previously identified opioid receptors in the carotid bodies and shown that their activation inhibits calcium influx into the chemosensitive cells. Given that the carotid bodies contribute to the drive to breathe and underpin the acute hypoxic ventilatory response, we hypothesized that ethanol and opioids may act synergistically in these peripheral sensory organs to further inhibit calcium influx and therefore inhibit ventilation.

Methods …

Genetic Targeting Of Adult Renshaw Cells Using A Calbindin 1 Destabilized Cre Allele For Intersection With Parvalbumin Or Engrailed1, Alicia R. Lane, Indeara C. Cogdell, Thomas M. Jessell, Jay B. Bikoff, Francisco J. Alvarez

Neuroscience, Cell Biology & Physiology Faculty Publications

Renshaw cells (RCs) are one of the most studied spinal interneurons; however, their roles in motor control remain enigmatic in part due to the lack of experimental models to interfere with RC function, specifically in adults. To overcome this limitation, we leveraged the distinct temporal regulation of Calbindin (Calb1) expression in RCs to create genetic models for timed RC manipulation. We used a Calb1 allele expressing a destabilized Cre (dgCre) theoretically active only upon trimethoprim (TMP) administration. TMP timing and dose influenced RC targeting efficiency, which was highest within the first three postnatal weeks, but specificity was low with …

Nsaids Naproxen, Ibuprofen, Salicylate, And Aspirin Inhibit Trpm7 Channels By Cytosolic Acidification, Rikki Chokshi, Orville Bennett, Tetyana Zhelay, J. Ashot Kozak

Neuroscience, Cell Biology & Physiology Faculty Publications

Non-steroidal anti-inflammatory drugs (NSAIDs) are used for relieving pain and inflammation accompanying numerous disease states. The primary therapeutic mechanism of these widely used drugs is the inhibition of cyclooxygenase 1 and 2 (COX1, 2) enzymes that catalyze the conversion of arachidonic acid into prostaglandins. At higher doses, NSAIDs are used for prevention of certain types of cancer and as experimental treatments for Alzheimer’s disease. In the immune system, various NSAIDs have been reported to influence neutrophil function and lymphocyte proliferation, and affect ion channels and cellular calcium homeostasis. Transient receptor potential melastatin 7 (TRPM7) cation channels are highly expressed in …

Placenta-Specific Slc38a2/Snat2 Knockdown Causes Fetal Growth Restriction In Mice, Owen R. Vaughan, Katarzyna Maksym, Elena Silva, Kenneth Barentsen, Russel V. Anthony, Sara L. Hillman, Thomas L. Brown, Rebecca Spencer, Anna L. David, Fredrick J. Rosario, Theresa L. Powell, Thomas Jansson

Neuroscience, Cell Biology & Physiology Faculty Publications

Fetal growth restriction (FGR) is a complication of pregnancy that reduces birth weight, markedly increases infant mortality and morbidity and is associated with later-life cardiometabolic disease. No specific treatment is available for FGR. Placentas of human FGR infants have low abundance of sodium-coupled neutral amino acid transporter 2 (Slc38a2/SNAT2), which supplies the fetus with amino acids required for growth. We determined the mechanistic role of placental Slc38a2/SNAT2 deficiency in the development of restricted fetal growth, hypothesizing that placenta-specific Slc38a2 knockdown causes FGR in mice. Using lentiviral transduction of blastocysts with a small hairpin RNA (shRNA), we achieved 59% knockdown of …

Current State Of Preeclampsia Mouse Models: Approaches, Relevance, And Standardization, Christopher A. Waker, Melissa R. Kaufman, Thomas L. Brown

Neuroscience, Cell Biology & Physiology Faculty Publications

Preeclampsia (PE) is a multisystemic, pregnancy-specific disorder and a leading cause of maternal and fetal death. PE is also associated with an increased risk for chronic morbidities later in life for mother and offspring. Abnormal placentation or placental function has been well-established as central to the genesis of PE; yet much remains to be determined about the factors involved in the development of this condition. Despite decades of investigation and many clinical trials, the only definitive treatment is parturition. To better understand the condition and identify potential targets preclinically, many approaches to simulate PE in mice have been developed and …

The Role Of Action Potential Waveform In Failure Of Excitation Contraction Coupling, Xueyong Wang, Murad Nawaz, Steve R.A. Burke, Roger Bannister, Brent D. Foy, Andrew A. Voss, Mark M. Rich

Neuroscience, Cell Biology & Physiology Faculty Publications

Excitation contraction coupling (ECC) is the process by which electrical excitation of muscle is converted into force generation. Depolarization of skeletal muscle resting potential contributes to failure of ECC in diseases such as periodic paralysis, ICU acquired weakness and possibly fatigue of muscle during vigorous exercise. When extracellular K+ is raised to depolarize the resting potential, failure of ECC occurs suddenly, over a range of several mV of resting potential. While some studies have hypothesized the sudden failure of ECC is due to all-or-none failure of excitation, other studies suggest failure of excitation is graded. Intracellular recordings of action potentials …

The Relationship Of Divine Forgiveness, Victim Forgiveness, And Physical Health Mediated By Stress, Lemuel Josiah C. Ragasajo

Senior Honors Theses

Though there is increasing evidence to support a relationship between forgiveness and physical health, certain subcategories of forgiveness, namely victim and divine forgiveness, are relatively understudied. This study seeks to add to the body of forgiveness literature by examining how divine and victim forgiveness relate to one’s physical health, and whether that relationship is mediated by stress. Furthermore, a literature review is included to detail how stress, a potential mediating variable between forgiveness and physical health, affects physical health. The results of the study reveal that victim forgiveness positively predicts physical health, but is not mediated by stress. In contrast, …

The Mechanism Underlying Transient Weakness In Myotonia Congenita, Jessica H. Myers, Kirsten Denman, Chris Dupont, Ahmed A. Hawash, Kevin R. Novak, Andrew Koesters, Manfred Grabner, Anamika Dayal, Andrew A. Voss, Mark M. Rich

Neuroscience, Cell Biology & Physiology Faculty Publications

In addition to the hallmark muscle stiffness, patients with recessive myotonia congenita (Becker disease) experience debilitating bouts of transient weakness that remain poorly understood despite years of study. We performed intracellular recordings from muscle of both genetic and pharmacologic mouse models of Becker disease to identify the mechanism underlying transient weakness. Our recordings reveal transient depolarizations (plateau potentials) of the membrane potential to -25 to -35 mV in the genetic and pharmacologic models of Becker disease. Both Na + and Ca 2+ currents contribute to plateau potentials. Na + persistent inward current (NaPIC) through Na V 1.4 channels is the …

A Mouse Model Of Huntington’S Disease Shows Altered Ultrastructure Of Transverse Tubules In Skeletal Muscle Fibers, Shannon H. Romer, Sabrina Metzger, Kristiana Peraza, Matthew C. Wright, D. Scott Jobe, Long-Sheng Song, Mark M. Rich, Brent D. Foy, Robert J. Talmadge, Andrew A. Voss

Neuroscience, Cell Biology & Physiology Faculty Publications

Huntington’s disease (HD) is a fatal and progressive condition with severe debilitating motor defects and muscle weakness. Although classically recognized as a neurodegenerative disorder, there is increasing evidence of cell autonomous toxicity in skeletal muscle. We recently demonstrated that skeletal muscle fibers from the R6/2 model mouse of HD have a decrease in specific membrane capacitance, suggesting a loss of transverse tubule (t-tubule) membrane in R6/2 muscle. A previous report also indicated that Cav1.1 current was reduced in R6/2 skeletal muscle, suggesting defects in excitation–contraction (EC) coupling. Thus, we hypothesized that a loss and/or disruption of the skeletal muscle t-tubule …

Neurophysiology Of Space Medicine: A Literature Review, Jose R. Velasquez

MEDI 9331 Scholarly Activities Clinical Years

Space medicine is becoming an essential and expanding clinical discipline. Acquiring a deeper and complete picture understanding of the multi-systemic response due to space on human health and function is essential to ensure the success of future space exploration. A comprehensive review of the literature was performed using PubMed and focused on the current neurophysiologic findings of the central nervous system’s response to space. Ground-based analogues, which mimic the effects of microgravity, and actual spaceflight studies have been used to analyze these physiologic adaptations to space. Overall, cerebellar, sensorimotor and vestibular brain regions seem to be affected the most. Through …

Measuring Mitochondrial Respiration In Vivo: From Mouse To Human, Arthur Orchanian, Brennan Schilling, Bruce Berkowitz Phd

Medical Student Research Symposium

Introduction: The mitochondrial energy ecosystem can be non-invasively interrogated in photoreceptors by combing a clinical tool, optical coherence tomography (OCT), with a mitochondrial protonophore (2,4 dinitrophenol, DNP). It remains unclear if only supra-clinical doses of DNP will be useful for mouse studies or if lower but clinically relevant doses of DNP would facilitate translation from mice to humans.

Methods: The experiment was a paired longitudinal design that took place over 2 days. On day 1, C57BL/6J mice were overnight dark adapted, then light-adapted for 5 h before OCT examination before regaining consciousness; a similar procedure was followed on day 2 …

Chronic Use Of Non-Medical Abdominal Compressors: Medical And Psychological Implications, Sawsan Edriss, Bushra Azom, Manar Edriss, Mustafa Edriss, Ann-Cathrin Guertler, Eva Waineo Md, Diane L. Levine Md

Medical Student Research Symposium

The popularity of waist cinchers, shapewear, abdominal binders, corsets, and waist trainers has increased in the population. Although corsets have been part of western fashion since the 18th century, abdominal compressors remain in style even today. In 2018, sales for shapewear worldwide were estimated at 2.26 billion USD. 1 Despite its popularity, shapewear safety and medical effects have not been widely studied.

In 1968, “Pantygirdle Syndrome” was described, attributing vulvitis, urethritis, and urinary tract infections to materials used from the “pantygirdle”. 2 The article describes that the girdle caused gastrointestinal symptoms with diaphragmatic and stomach displacement causing gastro-esophageal reflux disease …