Medical Physiology Commons^™

The Brain: A Panel, Ashima Brown, Jamila James, Cara Clark, Mikayla Rolda, Anna Le, Jourdan Lawrence, Brylea Huitt

Collin College Undergraduate Interdisciplinary Student Research Conference

Papers Presented:

"The Brain's Power on Personality Development" by Ashmima Brown, Jamila James, & Cara Clark

"The Brain's Highway" by Mikayla Rolda & Anna Le

Abstract: The peripheral nerves, which are made out of fibers or bundles of axons, include all the nerves beyond the brain and the spinal cord. They start from the edges of the central nerves, or spinal cord, and extend outwards to the periphery of the body. The main function of the peripheral nerves is to carry information from the central nervous system to the muscles and to important organs and then relay the sensory information …

Constitutive Activation Of Kappa Opioid Receptors At Ventral Tegmental Area Inhibitory Synapses Following Acute Stress., Abigail M Polter, Kelsey Barcomb, Rudy W Chen, Paige M Dingess, Nicholas M Graziane, Travis E Brown, Julie A Kauer

Pharmacology and Physiology Faculty Publications

Stressful experiences potently activate kappa opioid receptors (κORs). κORs in the ventral tegmental area regulate multiple aspects of dopaminergic and non-dopaminergic cell function. Here we show that at GABAergic synapses on rat VTA dopamine neurons, a single exposure to a brief cold-water swim stress induces prolonged activation of κORs. This is mediated by activation of the receptor during the stressor followed by a persistent, ligand-independent constitutive activation of the κOR itself. This lasting change in function is not seen at κORs at neighboring excitatory synapses, suggesting distinct time courses and mechanisms of regulation of different subsets of κORs. We also …

Diabetic Cardiomyopathy: An Immunometabolic Perspective., Paras K. Mishra, Wei Ying, Shyam Sundar Nandi, Gautam K. Bandyopadhyay, Kaushik K. Patel, Sushil K. Mahata

Journal Articles: Cellular & Integrative Physiology

The heart possesses a remarkable inherent capability to adapt itself to a wide array of genetic and extrinsic factors to maintain contractile function. Failure to sustain its compensatory responses results in cardiac dysfunction, leading to cardiomyopathy. Diabetic cardiomyopathy (DCM) is characterized by left ventricular hypertrophy and reduced diastolic function, with or without concurrent systolic dysfunction in the absence of hypertension and coronary artery disease. Changes in substrate metabolism, oxidative stress, endoplasmic reticulum stress, formation of extracellular matrix proteins, and advanced glycation end products constitute the early stage in DCM. These early events are followed by steatosis (accumulation of lipid droplets) …

Melatonin Modulates Inflammatory Response And Suppresses Burn-Induced Apoptotic Injury, Ganka Bekyarova, Milena Atanasova, Maria Tzaneva, Anelia Dimitrova

Journal of Mind and Medical Sciences

Introduction: Melatonin, the principal secretory product of the pineal gland, has antioxidant functions as a potent antioxidant and free radical scavenger. Objectives of the present study were to investigate the effect of melatonin against inflammatory response, burn-induced oxidative damage and apoptotic changes of rat liver. Methods: Melatonin (10 mg /kg, i.p.) was applied immediately after 30% of total body surface area (TBSA) burns on male Wistar rats. The level of malondialdehyde (MDA) as a marker of an oxidative stress was quantified by thiobarbituric method. Hepatic TNFα and IL-10 as inflammatory markers were assayed by ELISA. Using light immunоchistochemistry …

Enzyme-Dependent Fluorescence Recovery Of Nadh After Photobleaching To Assess Dehydrogenase Activity Of Isolated Perfused Hearts., Angel Moreno, Sarah Kuzmiak-Glancy, Rafael Jaimes, Matthew W Kay

Pharmacology and Physiology Faculty Publications

Reduction of NAD(+) by dehydrogenase enzymes to form NADH is a key component of cellular metabolism. In cellular preparations and isolated mitochondria suspensions, enzyme-dependent fluorescence recovery after photobleaching (ED-FRAP) of NADH has been shown to be an effective approach for measuring the rate of NADH production to assess dehydrogenase enzyme activity. Our objective was to demonstrate how dehydrogenase activity could be assessed within the myocardium of perfused hearts using NADH ED-FRAP. This was accomplished using a combination of high intensity UV pulses to photobleach epicardial NADH. Replenishment of epicardial NADH fluorescence was then imaged using low intensity UV illumination. NADH …

Proteome Dynamics During Postnatal Mouse Corpus Callosum Development., Alexander I Son, Xiaoqin Fu, Fumikazu Suto, Judy S Liu, Kazue Hashimoto-Torii, Masaaki Torii

Pharmacology and Physiology Faculty Publications

Formation of cortical connections requires the precise coordination of numerous discrete phases. This is particularly significant with regard to the corpus callosum, whose development undergoes several dynamic stages including the crossing of axon projections, elimination of exuberant projections, and myelination of established tracts. To comprehensively characterize the molecular events in this dynamic process, we set to determine the distinct temporal expression of proteins regulating the formation of the corpus callosum and their respective developmental functions. Mass spectrometry-based proteomic profiling was performed on early postnatal mouse corpus callosi, for which limited evidence has been obtained previously, using stable isotope of labeled …

Metabolic And Molecular Insights Into An Essential Role Of Nicotinamide Phosphoribosyltransferase., Li Q. Zhang, Leon Van Haandel, Min Xiong, Peixin Huang, Daniel P. Heruth, Chengpeng Bi, R Gaedigk, Xun Jiang, Ding-You Li, Gerald Wyckoff, Dmitry N. Grigoryev, Li Gao, Linheng Li, Min Wu, J Steven Leeder, Shui Qing Ye

Manuscripts, Articles, Book Chapters and Other Papers

Nicotinamide phosphoribosyltransferase (NAMPT) is a pleiotropic protein implicated in the pathogenesis of acute respiratory distress syndrome, aging, cancer, coronary heart diseases, diabetes, nonalcoholic fatty liver disease, obesity, rheumatoid arthritis, and sepsis. However, the underlying molecular mechanisms of NAMPT in these physiological and pathological processes are not fully understood. Here, we provide experimental evidence that a Nampt gene homozygous knockout (Nampt-/-) resulted in lethality at an early stage of mouse embryonic development and death within 5-10 days in adult mice accompanied by a 25.24±2.22% body weight loss, after the tamoxifen induction of NamptF/F × Cre mice. These results substantiate that Nampt …

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

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 EMG and dynamic MRI …

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 environmental risks relevant …

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.

Regulation Of Trpm7 By Cytosolic Mg2+ And Ph: Insights From Vsp Expression, Pavani Beesetty, Krystyna Blanka Wieczerzak, Tatyana Zhelay, Taku Kaitsuka, Masayuki Matsushita, J. Ashot Kozak

Neuroscience, Cell Biology & Physiology Faculty Publications

TRPM7 is an ion channel/protein kinase belonging to TRP melastatin and eEF2 kinase families. Under physiological conditions, most native TRPM7 channels are inactive, due to inhibition by cytoplasmic Mg2+, protons and polyamines. ITRPM7 is strongly potentiated when cell cytosol is depleted of Mg2+ or alkalinized. In Jurkat T cells, Mg2+ inhibition involves a high and a low affinity inhibitor sites, whereas proton inhibition involves only one site. Like many other TRP channels, TRPM7 is activated by PI(4,5)P2 and suppressed by its hydrolysis. Here we examined Mg2+ and pH inhibition of native TRPM7 channels in HEK293 cells overexpressing voltage-sensitive phospholipid phosphatase …

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

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

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

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 (BK^KO) 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 …

Resting State Functional Network Disruptions In A Kainic Acid Model Of Temporal Lobe Epilepsy., Ravnoor Singh Gill, Seyed M Mirsattari, L Stan Leung

Physiology and Pharmacology Publications

We studied the graph topological properties of brain networks derived from resting-state functional magnetic resonance imaging in a kainic acid induced model of temporal lobe epilepsy (TLE) in rats. Functional connectivity was determined by temporal correlation of the resting-state Blood Oxygen Level Dependent (BOLD) signals between two brain regions during 1.5% and 2% isoflurane, and analyzed as networks in epileptic and control rats. Graph theoretical analysis revealed a significant increase in functional connectivity between brain areas in epileptic than control rats, and the connected brain areas could be categorized as a limbic network and a default mode network (DMN). The …

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 …

Novel Orally Active Hydrogen Sulfide-Releasing Compound, Sg1002, Improves Left Ventricular Function And Survival In A Murine Model Of Ischemic Cardiomyopathy, Bharat Balan

Theses and Dissertations

Hydrogen sulfide (H₂S) is a gasotransmitter that has shown cardioprotective effects in the setting of myocardial injury such as acute myocardial infarction (MI) and pressure overload-induced heart failure. However, there are shortcomings in precision and control release from the use of traditional formulations of H₂S in the form of inorganic salts. In this thesis, we sought to determine if the novel, orally active, slow-releasing H₂S-compound SG1002 plays a role in attenuating MI-induced left ventricular (LV) dysfunction and adverse remodeling. We also evaluated the effect of SG1002 on changes in ECG parameters such as QT …

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 activity and TUNEL staining, which …