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A Role Of Central Nell2 In The Regulation Of Feeding Behavior In Rats., Jin Kwon Jeong, Jae Geun Kim, Han Rae Kim, Tae Hwan Lee, Jeong Woo Park, Byung Ju Lee 2017 George Washington University

A Role Of Central Nell2 In The Regulation Of Feeding Behavior In Rats., Jin Kwon Jeong, Jae Geun Kim, Han Rae Kim, Tae Hwan Lee, Jeong Woo Park, Byung Ju Lee

Pharmacology and Physiology Faculty Publications

A brain-enriched secreting signal peptide, NELL2, has been suggested to play multiple roles in the development, survival, and activity of neurons in mammal. We investigated here a possible involvement of central NELL2 in regulating feeding behavior and metabolism. In situ hybridization and an immunohistochemical approach were used to determine expression of NELL2 as well as its colocalization with proopiomelanocortin (POMC) and neuropeptide Y (NPY) in the rat hypothalamus. To investigate the effect of NELL2 on feeding behavior, 2 nmole of antisense NELL2 oligodeoxynucleotide was administered into the lateral ventricle of adult male rat brains for 6 consecutive days, and changes ...


Chemogenetic Stimulation Of The Hypoglossal Neurons Improves Upper Airway Patency, Thomas Curado, Kenneth Fishbein, Huy Pho, Michael Brennick, Olga Dergacheva, David Mendelowitz, +several additional authors 2017 George Washington University

Chemogenetic Stimulation Of The Hypoglossal Neurons Improves Upper Airway Patency, Thomas Curado, Kenneth Fishbein, Huy Pho, Michael Brennick, Olga Dergacheva, David Mendelowitz, +Several Additional Authors

Pharmacology and Physiology Faculty Publications

Obstructive sleep apnea (OSA) is characterized by recurrent upper airway obstruction during sleep. OSA leads to high cardiovascular morbidity and mortality. The pathogenesis of OSA has been linked to a defect in neuromuscular control of the pharynx. There is no effective pharmacotherapy for OSA. The objective of this study was to determine whether upper airway patency can be improved using chemogenetic approach by deploying designer receptors exclusively activated by designer drug (DREADD) in the hypoglossal motorneurons. DREADD (rAAV5-hSyn-hM3(Gq)-mCherry) and control virus (rAAV5-hSyn-EGFP) were stereotactically administered to the hypoglossal nucleus of C57BL/6J mice. In 6–8 weeks genioglossus ...


Oxidative Stress-Driven Parvalbumin Interneuron Impairment As A Common Mechanism In Models Of Schizophrenia, P Steullet, J Cabungcal, J Coyle, M Didriksen, K Gill, Anthony-Samuel LaMantia, +several additional authors 2017 George Washington University

Oxidative Stress-Driven Parvalbumin Interneuron Impairment As A Common Mechanism In Models Of Schizophrenia, P Steullet, J Cabungcal, J Coyle, M Didriksen, K Gill, Anthony-Samuel Lamantia, +Several Additional Authors

Pharmacology and Physiology Faculty Publications

Parvalbumin inhibitory interneurons (PVIs) are crucial for maintaining proper excitatory/inhibitory balance and high-frequency neuronal synchronization. Their activity supports critical developmental trajectories, sensory and cognitive processing, and social behavior. Despite heterogeneity in the etiology across schizophrenia and autism spectrum disorder, PVI circuits are altered in these psychiatric disorders. Identifying mechanism(s) underlying PVI deficits is essential to establish treatments targeting in particular cognition. On the basis of published and new data, we propose oxidative stress as a common pathological mechanism leading to PVI impairment in schizophrenia and some forms of autism. A series of animal models carrying genetic and/or ...


Amh/Mis As A Contraceptive That Protects The Ovarian Reserve During Chemotherapy, Motohiro Kano, Amanda E. Sosulski, LiHua Zhang, Hatice D. Saatcioglu, Dan Wang, Nicholas Nagykery, Mary E. Sabatini, Guangping Gao, Patricia K. Donahoe, David Pepin 2017 Massachusetts General Hospital

Amh/Mis As A Contraceptive That Protects The Ovarian Reserve During Chemotherapy, Motohiro Kano, Amanda E. Sosulski, Lihua Zhang, Hatice D. Saatcioglu, Dan Wang, Nicholas Nagykery, Mary E. Sabatini, Guangping Gao, Patricia K. Donahoe, David Pepin

Open Access Articles

The ovarian reserve represents the stock of quiescent primordial follicles in the ovary which is gradually depleted during a woman's reproductive lifespan, resulting in menopause. Mullerian inhibiting substance (MIS) (or anti-Mullerian hormone/AMH), which is produced by granulosa cells of growing follicles, has been proposed as a negative regulator of primordial follicle activation. Here we show that long-term parenteral administration of superphysiological doses of MIS, using either an adeno-associated virus serotype 9 (AAV9) gene therapy vector or recombinant protein, resulted in a complete arrest of folliculogenesis in mice. The ovaries of MIS-treated mice were smaller than those in controls ...


Genetic Targeting In Cerebellar Purkinje Cells: An Update., Anna Sługocka, Jan Wiaderkiewicz, Jaroslaw J Barski 2017 George Washington University

Genetic Targeting In Cerebellar Purkinje Cells: An Update., Anna Sługocka, Jan Wiaderkiewicz, Jaroslaw J Barski

Pharmacology and Physiology Faculty Publications

Since the last review paper published in Cerebellum in 2002 [1], there has been a substantial increase in the number of experiments utilizing transgenic manipulations in murine cerebellar Purkinje cells. Most of these approaches were made possible with the use of the Cre/loxP methodology and pcp2/L7 based Cre recombinase expressing transgenic mouse strains. This review aims to summarize all studies which used Purkinje cell specific transgenesis since the first use of mouse strain with Purkinje cell specific Cre expression in 2002.


Analysis Of Proprioceptive Sensory Innervation Of The Mouse Soleus: A Whole-Mount Muscle Approach, Martha Jean Sonner, Marie C. Walters, David R. Ladle 2017 Wright State University

Analysis Of Proprioceptive Sensory Innervation Of The Mouse Soleus: A Whole-Mount Muscle Approach, Martha Jean Sonner, Marie C. Walters, David R. Ladle

Neuroscience, Cell Biology & Physiology Faculty Publications

Muscle proprioceptive afferents provide feedback critical for successful execution of motor tasks via specialized mechanoreceptors housed within skeletal muscles: muscle spindles, supplied by group Ia and group II afferents, and Golgi tendon organs, supplied by group Ib afferents. The morphology of these proprioceptors and their associated afferents has been studied extensively in the cat soleus, and to a lesser degree, in the rat; however, quantitative analyses of proprioceptive innervation in the mouse soleus are comparatively limited. The present study employed genetically-encoded fluorescent reporting systems to label and analyze muscle spindles, Golgi tendon organs, and the proprioceptive sensory neuron subpopulations supplying ...


Diversity And Plasticity In Signaling Pathways That Regulate Smooth Muscle Responsiveness: Paradigms And Paradoxes For The Myosin Phosphatase, The Master Regulator Of Smooth Muscle Contraction., Masumi Eto, Toshio Kitazawa 2017 Thomas Jefferson University

Diversity And Plasticity In Signaling Pathways That Regulate Smooth Muscle Responsiveness: Paradigms And Paradoxes For The Myosin Phosphatase, The Master Regulator Of Smooth Muscle Contraction., Masumi Eto, Toshio Kitazawa

Department of Molecular Physiology and Biophysics Faculty Papers

A hallmark of smooth muscle cells is their ability to adapt their functions to meet temporal and chronic fluctuations in their demands. These functions include force development and growth. Understanding the mechanisms underlying the functional plasticity of smooth muscles, the major constituent of organ walls, is fundamental to elucidating pathophysiological rationales of failures of organ functions. Also, the knowledge is expected to facilitate devising innovative strategies that more precisely monitor and normalize organ functions by targeting individual smooth muscles. Evidence has established a current paradigm that the myosin light chain phosphatase (MLCP) is a master regulator of smooth muscle responsiveness ...


On The Origin Of Superoxide Dismutase: An Evolutionary Perspective Of Superoxide-Mediated Redox Signaling., Adam J. Case 2017 University of Nebraska Medical Center

On The Origin Of Superoxide Dismutase: An Evolutionary Perspective Of Superoxide-Mediated Redox Signaling., Adam J. Case

Journal Articles: Cellular & Integrative Physiology

The field of free radical biology originated with the discovery of superoxide dismutase (SOD) in 1969. Over the last 5 decades, a plethora of research has been performed in species ranging from bacteria to mammals that has elucidated the molecular reaction, subcellular location, and specific isoforms of SOD. However, while humans have only begun to study this class of enzymes over the past 50 years, it has been estimated that these enzymes have existed for billions of years, and may be some of the original enzymes found in primitive life. As life evolved over this expanse of time, these enzymes ...


Survival And Growth Of C57bl/6j Mice Lacking The Bk Channel, Kcnma1: Lower Adult Body Weight Occurs Together With Higher Body Fat, Susan T. Halm, Michael A. Bottomley, Mohammed M. Almutairi, Mauricio Di Fulvio, Dan R. Halm 2017 Wright State University - Main Campus

Survival And Growth Of C57bl/6j Mice Lacking The Bk Channel, Kcnma1: Lower Adult Body Weight Occurs Together With Higher Body Fat, Susan T. Halm, Michael A. Bottomley, Mohammed M. Almutairi, Mauricio Di Fulvio, Dan R. Halm

Neuroscience, Cell Biology & Physiology Faculty Publications

Big conductance potassium (BK) channels contribute to K+ flow and electrical behavior in many cell types. Mice made null for the gene (Kcnma1) producing the BK channel (BKKO) exhibit numerous deficits in physiological functions. Breeding mice lacking a single allele of Kcnma1 (C57BL/6J background) had litter sizes of approximately eight pups. For the period of maternal care (P0– P21), pup deaths peaked at P1 with a second less severe interval of death peaking near P13. Early deaths were twice as likely during a 20-month period of building construction compared with the quiescent period after cessation of construction. Births ...


Uncorrelated Neural Firing In Mouse Visual Cortex During Spontaneous Retinal Waves, Matthew Colonnese, Jing Shen, Yasunobu Murata 2017 George Washington University

Uncorrelated Neural Firing In Mouse Visual Cortex During Spontaneous Retinal Waves, Matthew Colonnese, Jing Shen, Yasunobu Murata

Pharmacology and Physiology Faculty Publications

Synchronous firing among the elements of forming circuits is critical for stabilization of synapses. Understanding the nature of these local network interactions during development can inform models of circuit formation. Within cortex, spontaneous activity changes throughout development. Unlike the adult, early spontaneous activity occurs in discontinuous population bursts separated by long silent periods, suggesting a high degree of local synchrony. However, whether the micro-patterning of activity within early bursts is unique to this early age and specifically tuned for early development is poorly understood, particularly within the column. To study this we used single-shank multi-electrode array recordings of spontaneous activity ...


Effects Of Neonatal Supplemental Oxygen And High Fat Diet On Weight Gain, Ventricular Hypertrophy And Contractility, Shreya Chandrasekar, Melissa L. Bates, Shilpa Vellookunnel, Michael J. Hoover, Madison E. Sturgeon, Austin Murphy 2017 University of Iowa

Effects Of Neonatal Supplemental Oxygen And High Fat Diet On Weight Gain, Ventricular Hypertrophy And Contractility, Shreya Chandrasekar, Melissa L. Bates, Shilpa Vellookunnel, Michael J. Hoover, Madison E. Sturgeon, Austin Murphy

Honors Theses at the University of Iowa

Premature birth represents about 13% of live births each year. Since lungs of these infants are underdeveloped, they receive supplemental oxygen right after birth, but little is known about its effects on the development of normal physiological responses and whether it impacts long-term cardio-metabolic function. Based on previous studies from our lab that showed increased pulse wave velocity in 12 month old rats exposed to neonatal supplemental oxygen, we hypothesized that neonatal exposure to supplemental oxygen causes cardiac hypertrophy and decreased left ventricular contractility. We also hypothesized that these effects to supplemental oxygen would be enhanced by 10 weeks on ...


Combatting The Organ Deficit, Jessica Berg 2016 University of Wyoming

Combatting The Organ Deficit, Jessica Berg

Honors Theses AY 16/17

Since its beginning in 1954 organ transplantation has become the leading life-saving treatment worldwide for end-stage organ failure. In the past few decades organ transplantation has become so successful that now the number of people in need of a life-saving organ vastly outnumbers the supply of organs available. If this deficit remains unaddressed the number of people that die each day due to organ failure will increase exponentially. Fortunately, this is a problem that can be solved from many angles.

This paper will present possible solutions to the organ crisis by examining the possible positive effects of implementing a mandated ...


Cardiac Specific Overexpression Of Mitochondrial Omi/Htra2 Induces Myocardial Apoptosis And Cardiac Dysfunction., Ke Wang, Yuexing Yuan, Xin Liu, Wayne Bond Lau, Lin Zuo, Xiaoliang Wang, Lu Ma, Kun Jiao, Jianyu Shang, Wen Wang, Xinliang Ma, Huirong Liu 2016 Capital Medical University

Cardiac Specific Overexpression Of Mitochondrial Omi/Htra2 Induces Myocardial Apoptosis And Cardiac Dysfunction., Ke Wang, Yuexing Yuan, Xin Liu, Wayne Bond Lau, Lin Zuo, Xiaoliang Wang, Lu Ma, Kun Jiao, Jianyu Shang, Wen Wang, Xinliang Ma, Huirong Liu

Department of Emergency Medicine Faculty Papers

Myocardial apoptosis is a significant problem underlying ischemic heart disease. We previously reported significantly elevated expression of cytoplasmic Omi/HtrA2, triggers cardiomyocytes apoptosis. However, whether increased Omi/HtrA2 within mitochondria itself influences myocardial survival in vivo is unknown. We aim to observe the effects of mitochondria-specific, not cytoplasmic, Omi/HtrA2 on myocardial apoptosis and cardiac function. Transgenic mice overexpressing cardiac-specific mitochondrial Omi/HtrA2 were generated and they had increased myocardial apoptosis, decreased systolic and diastolic function, and decreased left ventricular remodeling. Transiently or stably overexpression of mitochondria Omi/HtrA2 in H9C2 cells enhance apoptosis as evidenced by elevated caspase-3, -9 ...


Role Of Occludin In The Regulation Of Epithelial Tight Junctions, Bhargavi Manda 2016 University of Tennessee Health Science Center

Role Of Occludin In The Regulation Of Epithelial Tight Junctions, Bhargavi Manda

Theses and Dissertations (ETD)

Tight junctions (TJ) constitute the primary component of epithelial barrier function, a disruption of which is involved in the pathogenesis of many gastrointestinal, pulmonary and renal diseases. Occludin is the major transmembrane protein of TJ, a deletion of which leads to a complex phenotype including chronic inflammation in several epithelial tissues of occludin deficient mice and poor TJ integrity in epithelial cell lines. Its down regulation was seen in Crohn’s disease, tumors of the colon, brain, endometrium and breast cancer. Occludin is also known to be a target that enables Hepatitis C Virus infection and bacterial pathogenesis. But the ...


Dissecting The Physiological Roles Of Ulk1/2 In The Mouse Brain, Bo Wang 2016 University of Tennessee Health Science Center

Dissecting The Physiological Roles Of Ulk1/2 In The Mouse Brain, Bo Wang

Theses and Dissertations (ETD)

Mammalian UNC-51–like kinases 1 and 2 (ULK1 and ULK2), Caenorhabditis elegans UNC-51 and Drosophila melanogaster Atg1 are redundant serine/threonine kinases that regulate flux through the autophagy pathway in response to various types of cellular stress. C. elegans UNC-51 and D. melanogaster Atg1 also promote axonal growth and defasciculation, and disruption of these genes results in defects in axon guidance in invertebrates. Germline Ulk1/2-deficient mice die perinatally. Therefore, we used a conditional-knockout approach to investigate the roles of ULK1/2 in the brain. Mice lacking Ulk1 and Ulk2 in their central nervous systems (CNS) showed defects in axonal ...


Seeing The Invisible: Revealing Atrial Ablation Lesions Using Hyperspectral Imaging Approach, Narine Muselimyan, Luther Swift, Huda Asfour, Tigran Chahbazian, Ramesh Mazhari, Marco Mercader, Narine Sarvazyan 2016 George Washington University

Seeing The Invisible: Revealing Atrial Ablation Lesions Using Hyperspectral Imaging Approach, Narine Muselimyan, Luther Swift, Huda Asfour, Tigran Chahbazian, Ramesh Mazhari, Marco Mercader, Narine Sarvazyan

Pharmacology and Physiology Faculty Publications

Background

Currently, there are limited means for high-resolution monitoring of tissue injury during radiofrequency ablation procedures.

Objective

To develop the next generation of visualization catheters that can reveal irreversible atrial muscle damage caused by ablation and identify viability gaps between the lesions.

Methods

Radiofrequency lesions were placed on the endocardial surfaces of excised human and bovine atria and left ventricles of blood perfused rat hearts. Tissue was illuminated with 365nm light and a series of images were acquired from individual spectral bands within 420-720nm range. By extracting spectral profiles of individual pixels and spectral unmixing, the relative contribution of ablated ...


The Role Of The Mir-200 Family On The Tumor Suppressor Rassf2 And The Effect On Mapk Pathway Activity In Colorectal Cancer., Jane V. Carter 2016 University of Louisville

The Role Of The Mir-200 Family On The Tumor Suppressor Rassf2 And The Effect On Mapk Pathway Activity In Colorectal Cancer., Jane V. Carter

Electronic Theses and Dissertations

This dissertation investigated the role of the miR-200 family in normal colon epithelial (CCD 841) and Dukes’ C (HT-29) colorectal cancer (CRC) cell lines. Our aim was to characterize expression of the miR-200 family (miR-200a, miR-200b, miR-200c, miR-141, and miR-429) in colorectal cell lines, study their effect on the tumor suppressor Ras Associated Domain-Containing Protein (RASSF) 2 and on subsequent activity within the mitogen-activated protein kinase (MAPK) signaling pathway. We wanted to determine whether regulation of miR-200 family members could change cell behavior towards more “cancer-like” in a normal colon epithelium (CCD 841) cell line, or less “cancer-like” in a ...


Evaluating Cardiovascular Dysfunction During Increased Activity And Exercise Rehabilitation Following Incomplete Thoracic Spinal Cord Injury In The Adult Rat., Kathryn A. Harman 2016 University of Louisville

Evaluating Cardiovascular Dysfunction During Increased Activity And Exercise Rehabilitation Following Incomplete Thoracic Spinal Cord Injury In The Adult Rat., Kathryn A. Harman

Electronic Theses and Dissertations

Spinal cord injury (SCI) results in whole-body dysfunction. While the majority of SCI research is focused on improving locomotor function after injury, cardiovascular (CV) disease continues to be the leading cause of morbidity in the chronic SCI patient population. The combination of injury-induced destruction of autonomic pathways, maladaptive plasticity within lumbosacral circuits, and the progressive decline in physical fitness contribute to the poor CV status of SCI individuals. Currently, there is little emphasis on implementing appropriately-timed acute rehabilitation techniques aimed to curtail maladaptive remodeling and improve CV outcomes. Furthermore, no pre-clinical or clinical studies have investigated the most appropriate time-course ...


Neuroprotective Molecules And Strategies In A Rat Model Of Neonatal Hypoxic Ischemic Encephalopathy, Brandon Joseph Dixon 2016 Loma Linda University

Neuroprotective Molecules And Strategies In A Rat Model Of Neonatal Hypoxic Ischemic Encephalopathy, Brandon Joseph Dixon

Loma Linda University Electronic Theses, Dissertations & Projects

Neonatal hypoxic ischemic encephalopathy (HIE) is a devastating disease that primarily causes neuronal and white matter injury and is among the leading cause of death among infants. Currently there are no well-established treatments; thus, it is important to understand the pathophysiology of the disease and elucidate complications that are creating a gap between basic science and clinical translation. In the development of neuroprotective strategies and translation of experimental results in HIE, there are many limitations and challenges to master based on an appropriate study design, drug delivery properties, dosage, and use in neonates. Since there are no established therapies for ...


Development Of Activity In The Mouse Visual Cortex., Jing Shen, Matthew T Colonnese 2016 George Washington University

Development Of Activity In The Mouse Visual Cortex., Jing Shen, Matthew T Colonnese

Pharmacology and Physiology Faculty Publications

No abstract provided.


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