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1. Adenylyl cyclases types 1 and 8 promote pro-survival pathways after ethanol exposure in the neonatal brain

Author

Alana C. Conti, Chainllie Young, John W. Olney, and Louis J. Muglia

Subjects
Fetal alcohol syndrome, Striatum, Apoptosis, Ethanol, Phosphorylation, Caspase-3, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Although a wide range of developmental disabilities following fetal alcohol exposure are observed clinically, the molecular factors that determine the severity of these sequelae remain undefined. In mice exposed to ethanol, deletion of adenylyl cyclases (ACs) 1 and 8 exacerbates the neuroapoptosis that occurs in a prolonged post-treatment period; however, it remains unclear whether AC1 and AC8 are critical to the primary or secondary mechanisms underlying ethanol-induced neurodegeneration. Here we demonstrate that mice lacking AC1 and AC8 (DKO) display significantly increased apoptosis in the striatum, a region sensitive to neuroapoptosis in the acute post-treatment period, compared to WT controls. The enhanced neuroapoptotic response observed in the striatum of DKO mice is accompanied by significant reductions in phosphorylation of known pro-survival proteins, insulin receptor substrate-1 (IRS-1), Akt and extracellular signal-regulated kinases (ERKs). These data suggest that AC1/AC8 are crucial activators of cell survival signaling pathways acutely following ethanol exposure and represent molecular factors that may directly modulate the severity of symptoms associated with Fetal Alcohol Syndrome.

Published
2009
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2. Apoptotic neurodegeneration induced by ethanol in neonatal mice is associated with profound learning/memory deficits in juveniles followed by progressive functional recovery in adults

Author

David F. Wozniak, Richard E. Hartman, Maureen P. Boyle, Sherri K. Vogt, Ashley R. Brooks, Tatyana Tenkova, Chainllie Young, John W. Olney, and Louis J. Muglia

Subjects
Apoptosis, Behavior, Fetal Alcohol Syndrome, Hippocampus, Mice, Thalamus, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Administration of ethanol to rodents during the synaptogenesis period induces extensive apoptotic neurodegeneration in the developing brain. This neurotoxicity may explain the reduced brain mass and neurobehavioral disturbances in human Fetal Alcohol Syndrome (FAS). Here, we report binge-like exposure of infant mice to ethanol on a single postnatal day triggered apoptotic death of neurons from diencephalic structures that comprise an extended hippocampal circuit important for spatial learning and memory. The ethanol exposure paradigm yielding these neuronal losses caused profound impairments in spatial learning and memory at 1 month of age. This impairment was significantly attenuated during subsequent development, indicating recovery of function. Recovery was not associated with increased neurogenesis, suggesting plastic reorganization of neuronal networks compensated for early neuronal losses. We hypothesize that neuroapoptotic damage in homologous regions of human brain underlies cognitive deficits in FAS and the human brain of FAS victims has a similar capacity to effect functional recovery.

Published
2004
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3. Ethanol-Induced Caspase-3 Activation in the in Vivo Developing Mouse Brain

Author

John W. Olney, Tatyana Tenkova, Krikor Dikranian, Louis J. Muglia, Walter J. Jermakowicz, Cleta D'Sa, and Kevin A. Roth

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Recently several methods have been described for triggering extensive apoptotic neurodegeneration in the developing in vivo mammalian brain. These methods include treatment with drugs that block NMDA glutamate receptors, drugs that promote GABAA neurotransmission, or treatment with ethanol, which has both NMDA antagonist and GABAmimetic properties. A single intoxication episode induced by any of these agents is sufficient to cause widespread neurodegeneration throughout many brain regions. The cell death process transpires rapidly from early to late stages within several hours. As the neurons die, they become TUNEL positive and show, by both light and electron microscopy, all of the classical morphological characteristics of apoptosis. In the present study, using immunocytochemical methods, we document that ethanol intoxication of 7-day-old infant mice causes a widespread pattern of caspase-3 activation corresponding to the pattern of apoptotic neurodegeneration that is occurring simultaneously.

Published
2002
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4. Contributors

Author

Heide Aungst, Philippe Backeljauw, Jeffrey Baron, Tadej Battelino, Andrew J. Bauer, David T. Breault, Yee-Ming Chan, Steven D. Chernausek, David W. Cooke, Sarah C. Couch, Stephen R. Daniels, Mehul T. Dattani, Diva D. De Leon, Johnny Deladoey, Leo Dunkel, Brian J. Feldman, Lauren Fishbein, Christa E. Flück, Claus Højbjerg Gravholt, Siri Atma W. Greeley, Adda Grimberg, Michael J. Haller, Joan C. Han, Helen N. Jones, Alexander A.L. Jorge, Paul Kruszka, Bassil Kublaoui, Peter A. Lee, Michael A. Levine, David Maahs, Joseph A. Majzoub, Tani Malhotra, Mary K. McCauley, Ram K. Menon, Sam Mesiano, Walter L. Miller, Louis J. Muglia, Jon Nakamoto, Bimota Nambam, Mark R. Palmert, Louis H. Philipson, Moshe Phillip, Sally Radovick, Scott Rivkees, Allen W. Root, Robert L. Rosenfield, Stephen M. Rosenthal, Desmond Schatz, Mark A. Sperling, Abhinash Srivatsa, Charles A. Stanley, Constantine A. Stratakis, William V. Tamborlane, Paul Thornton, Massimo Trucco, Guy Van Vliet, Julia Elisabeth von Oettingen, Steven G. Waguespack, Ram Weiss, William E. Winter, Amy B. Wisniewski, Selma Feldman Witchel, and Joseph I. Wolfsdorf

Published
2021
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5. Fetal-Maternal Endocrinology and Parturition

Author

Tani Malhotra, Helen Jones, Sam Mesiano, Louis J. Muglia, and Heide Aungst

Subjects
Pregnancy, Fetus, medicine.medical_specialty, business.industry, Obstetrics, Uterus, Endometrium, medicine.disease, Maternal Physiology, Preeclampsia, medicine.anatomical_structure, embryonic structures, Medicine, Conceptus, Gestation, business, reproductive and urinary physiology
Abstract

The successful establishment, maintenance, and completion of pregnancy are essential for human development and survival. A series of structural and physiologic changes in the mother and fetus ensue, including implantation of the developing embryo into the endometrium; its avoidance of immunologic rejection by the maternal immune system; adaptation of the maternal uterus to sustain a pregnancy; and specific changes in maternal physiology to meet the nutritional, metabolic, and physical needs of the growing conceptus. Moreover, the duration of gestation must be optimized to ensure survival of both the mother and fetus. In this chapter, we provide an overview of these stages of pregnancy required to deliver the human newborn at term or lead to adverse pregnancy outcomes, such as preterm birth, preeclampsia, and growth restriction.

Published
2021
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6. Natural Selection Has Differentiated the Progesterone Receptor among Human Populations

Author

Xiaobin Wang, Louis J. Muglia, Michael Snyder, Gary M. Shaw, Xiumei Hong, Jingjing Li, Sam Mesiano, and David K. Stevenson

Subjects
0301 basic medicine, Population, Locus (genetics), Neanderthal genome project, Biology, Balancing selection, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, Asian People, Genetics, Animals, Humans, Allele, Selection, Genetic, Evolutionary dynamics, education, skin and connective tissue diseases, Genetics (clinical), Alleles, Neanderthals, education.field_of_study, Genetic diversity, Natural selection, 030104 developmental biology, Evolutionary biology, Female, Receptors, Progesterone, Genome-Wide Association Study
Abstract

The progesterone receptor (PGR) plays a central role in maintaining pregnancy and is significantly associated with medical conditions such as preterm birth that affects 12.6% of all the births in U.S. PGR has been evolving rapidly since the common ancestor of human and chimpanzee, and we herein investigated evolutionary dynamics of PGR during recent human migration and population differentiation. Our study revealed substantial population differentiation at the PGR locus driven by natural selection, where very recent positive selection in East Asians has substantially decreased its genetic diversity by nearly fixing evolutionarily novel alleles. On the contrary, in European populations, the PGR locus has been promoted to a highly polymorphic state likely due to balancing selection. Integrating transcriptome data across multiple tissue types together with large-scale genome-wide association data for preterm birth, our study demonstrated the consequence of the selection event in East Asians on remodeling PGR expression specifically in the ovary and determined a significant association of early spontaneous preterm birth with the evolutionarily selected variants. To reconstruct its evolutionary trajectory on the human lineage, we observed substantial differentiation between modern and archaic humans at the PGR locus, including fixation of a deleterious missense allele in the Neanderthal genome that was later introgressed in modern human populations. Taken together, our study revealed substantial evolutionary innovation in PGR even during very recent human evolution, and its different forms among human populations likely result in differential susceptibility to progesterone-associated disease conditions including preterm birth.

Published
2018

7. Fetal and Neonatal Adrenocortical Physiology

Author

Louis J. Muglia and Kristi L. Watterberg

Subjects
0301 basic medicine, 03 medical and health sciences, Fetus, 030104 developmental biology, 0302 clinical medicine, business.industry, Physiology, Medicine, business, 030217 neurology & neurosurgery
Published
2017
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8. Contributors

Author

Soraya Abbasi, James Abbey, N. Scott Adzick, Sun-Young Ahn, Kurt H. Albertine, Karel Allegaert, Seth L. Alper, Gabriel Altit, Steven M. Altschuler, Ruben E. Alvaro, Jennifer M.H. Amorosa, Kelsey L. Anbuhl, Claus Yding Andersen, Richard A. Anderson, David J. Askenazi, Richard Lambert Auten, Julie Autmizguine, Timur Azhibekov, Stephen A. Back, Jérôme Badaut, Peter Russell Baker, Philip L. Ballard, Eduardo H. Bancalari, Tatiana Barichello, Frederick Battaglia, Michel Baum, Simon Beggs, Edward F. Bell, Corinne Benchimol, Manon J.N.L. Benders, Laura Bennet, Phillip R. Bennett, Melvin Berger, Wolfgang Bernhard, John F. Bertram, Vikrant K. Bhosle, Vinod K. Bhutani, M. Jane Black, Joseph M. Bliss, David L. Bolender, Joline E. Brandenburg, Delma L. Broussard, Laura Davidson Brown, Douglas G. Burrin, Barbara Cannon, Michael Caplan, Susan E. Carlson, David P. Carlton, Georgina Caruana, William J. Cashore, Piya Chaemsaithong, Noppadol Chaiyasit, Jennifer R. Charlton, Carol L. Cheatham, Sylvain Chemtob, Yi-Yung Chen, Robert L. Chevalier, Sadhana Chheda, Andrew J. Childs, Robert D. Christensen, Alison Chu, David H. Chu, Maria Roberta Cilio, David A. Clark, Jane Cleary-Goldman, Ethel G. Clemente, John A. Clements, Ronald I. Clyman, Susan S. Cohen, John Colombo, Richard M. Cowett, Peter A. Crawford, James E. Crowe, Luise A. Cullen-McEwen, Wayne S. Cutfield, Mary E. D'Alton, Enrico Danzer, Christophe Delacourt, Sherin U. Devaskar, Thomas G. Diacovo, Nikolina Docheva, John P. Dormans, Kevin Dysart, Afif El-Khuffash, Peter James Ellis, Kerry McGarr Empey, Baris Ercal, Melinda Erdős, Robert P. Erickson, Mohamed A. Fahim, Arij Faksh, Hans-Georg Frank, Philippe S. Friedlich, Jed Friedman, Yuansheng Gao, Marianne Garland, Donna Geddes, Michael K. Georgieff, Jason Gien, Dino A. Giussani, Armond S. Goldman, Efrén González, Misty Good, Denis M. Grant, Lucy R. Green, Emmanouil Grigoriou, Adda Grimberg, Ian Gross, Ruth E. Grunau, Jean-Pierre Guignard, Alistair Jan Gunn, Nursen Gurtunca, Alice Hadchouel, Gabriel G. Haddad, Henrik Hagberg, Thomas Hale, K. Michael Hambidge, Cathy Hammerman, Thor Willy Ruud Hansen, Mark A. Hanson, Richard Harding, Mary Catherine Harris, Peter Hartmann, Foteini Hassiotou, Guttorm Haugen, Colin P. Hawkes, William W. Hay, Christina E. Hayward, Vivi M. Heine, Ann Hellström, Michael A. Helmrath, Karen D. Hendricks-Muñoz, Emilio Herrera, Michael J. Hiatt, Steven B. Hoath, Stuart B. Hooper, Stephen A. Huang, Silvia Iacobellli, Terrie E. Inder, M. Luisa Iruela-Arispe, Sudarshan R. Jadcherla, Deepak Jain, Thomas Jansson, John Lynn Jefferies, Jennifer G. Jetton, Alan H. Jobe, Lois H. Johnson, Richard B. Johnston, Rebecca Lee Jones, Pedro A. Jose, Satish C. Kalhan, Suhas G. Kallapur, Michael Kaplan, Stanley Kaplan, Heidi Eigenrauch Karpen, Saul J. Karpen, S. Ananth Karumanchi, Frederick J. Kaskel, Anup C. Katheria, Lorraine E. Levitt Katz, Susan E. Keeney, Steven E. Kern, Shirin Khanjani, Laurie E. Kilpatrick, Chang-Ryul Kim, John P. Kinsella, Torvid Kiserud, Joyce M. Koenig, Tobias R. Kollmann, Jay K. Kolls, Nancy F. Krebs, Thomas J. Kulik, Jessica Katz Kutikov, Satyan Lakshminrusimha, Angelo A. Lamola, Miguel Angel Lasunción, Pascal M. Lavoie, Tucker W. LeBien, Mary M. Lee, Matthew K. Lee, Yvonne K. Lee, Sandra Leibel, Fred Levine, Ofer Levy, Yang Liu, Steven Lobritto, Cynthia A. Loomis, Colleen A. Lopez, David A. MacIntyre, Maxime M. Mahe, Akhil Maheshwari, Anastasiya Mankouski, Carlos B. Mantilla, Arnaud Marchant, Kara Gross Margolis, M. Michele Mariscalco, László Maródi, Karel Maršál, Richard J. Martin, Douglas G. Matsell, Dwight E. Matthews, Harry J. McArdle, James L. McManaman, Patrick J. McNamara, Patrick S. McQuillen, Tim C. McQuinn, Judith S. Mercer, Giacomo Meschia, Steven P. Miller, Parviz Minoo, Paul Monagle, Jacopo P. Mortola, Louis J. Muglia, Upender K. Munshi, Ran Namgung, Sumana Narasimhan, Jan Nedergaard, Josef Neu, Sanjay K. Nigam, Lawrence M. Nogee, Shahab Noori, Barbara M. O'Brien, Robin K. Ohls, Henar Ortega-Senovilla, Justin M. O'Sullivan, Sarah A. Owusu, Abhijeet Pal, Howard B. Panitch, Anna A. Penn, Raymond B. Penn, Cameron Pernia, Anthony F. Philipps, Joseph A. Picoraro, Francesco Pisani, David Pleasure, Jeanette R. Pleasure, Samuel J. Pleasure, Scott L. Pomeroy, Martin Post, Y.S. Prakash, Joshua D. Prozialeck, Theodore J. Pysher, Raymond Quigley, Marlene Rabinovitch, Thomas M. Raffay, J. Usha Raj, Haley Ramsey, Sarosh Rana, Tara Marie Randis, Manon Ranger, Adam J. Ratner, Timothy R.H. Regnault, Henrique Rigatto, Natalie E. Rintoul, Roberto Romero, James C. Rose, Charles R. Rosenfeld, A. Catharine Ross, Henry J. Rozycki, Thomas D. Ryan, Rakesh Sahni, Eniko Sajti, Harvey B. Sarnat, Lisa M. Satlin, Ola Didrik Saugstad, William Schierding, Frank C. Schmalstieg, George J. Schwartz, Jeffrey Schwartz, Jeffrey L. Segar, David T. Selewski, Istvan Seri, Thomas H. Shaffer, Kara N. Shah, Martin J. Shearer, Sharareh Shojaie, Noah F. Shroyer, Colin P. Sibley, Gary C. Sieck, Rebecca A. Simmons, Emidio M. Sivieri, Francine G. Smith, Lois E.H. Smith, Ian M. Smyth, Brian S. Snarr, Evan Y. Snyder, Martha Sola-Visner, Michael J. Solhaug, Mark A. Sperling, Lakshmi Srinivasan, Andreas Stahl, Charles A. Stanley, Robin H. Steinhorn, Barbara S. Stonestreet, Janette F. Strasburger, Dennis M. Styne, Lori Sussel, Emily W.Y. Tam, Libo Tan, Claire Thornton, Daniel J. Tollin, Beáta Tóth, Jeffrey A. Towbin, Ashley Trocle, William E. Truog, Reginald C. Tsang, Kristin M. Uhler, John N. Van Den Anker, Johannes (Hans) B. van Goudoever, Susan J. Vannucci, Mark H. Vickers, Daniela Virgintino, Joseph J. Volpe, Neeta L. Vora, Neha V. Vyas, Annette Wacker-Gussmann, Megan J. Wallace, Brian H. Walsh, Alice M. Wang, David Warburton, Robert M. Ward, Kristi L. Watterberg, Lynne A. Werner, Barry K. Wershil, Susan E. Wert, Andy Wessels, Jeffrey A. Whitsett, Michael Wise, Matthias T. Wolf, Marla R. Wolfson, Hector R. Wong, James L. Wynn, Lami Yeo, Stephen Yip, Bradley A Yoder, Mervin C. Yoder, Momoko Yoshimoto, Christopher J. Yuskaitis, Dan Zhou, and Ann Zovein

Published
2017
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9. Signatures of natural selection on genetic variants affecting complex human traits

Author

Louis J. Muglia, Joshua M. Akey, Ranajit Chakraborty, Scott M. Williams, and Ge Zhang

Subjects
Genetics, education.field_of_study, Natural selection, Genome-wide association, lcsh:QH426-470, Directional selection, Population, Pharmaceutical Science, Genome-wide association study, Polygenic adaptation, Biology, Complex traits, Special issue: evolutionary genomics, lcsh:Genetics, Evolutionary biology, Pleiotropy, education, Molecular Biology, Allele frequency, Selection (genetic algorithm), Biotechnology, Common disease-common variant
Abstract

It has recently been hypothesized that polygenic adaptation, resulting in modest allele frequency changes at many loci, could be a major mechanism behind the adaptation of complex phenotypes in human populations. Here we leverage the large number of variants that have been identified through genome-wide association (GWA) studies to comprehensively study signatures of natural selection on genetic variants associated with complex traits. Using population differentiation based methods, such as FST and phylogenetic branch length analyses, we systematically examined nearly 1300 SNPs associated with 38 complex phenotypes. Instead of detecting selection signatures at individual variants, we aimed to identify combined evidence of natural selection by aggregating signals across many trait associated SNPs. Our results have revealed some general features of polygenic selection on complex traits associated variants. First, natural selection acting on standing variants associated with complex traits is a common phenomenon. Second, characteristics of selection for different polygenic traits vary both temporarily and geographically. Third, some studied traits (e.g. height and urate level) could have been the primary targets of selection, as indicated by the significant correlation between the effect sizes and the estimated strength of selection in the trait associated variants; however, for most traits, the allele frequency changes in trait associated variants might have been driven by the selection on other correlated phenotypes. Fourth, the changes in allele frequencies as a result of selection can be highly stochastic, such that, polygenic adaptation may accelerate differentiation in allele frequencies among populations, but generally does not produce predictable directional changes. Fifth, multiple mechanisms (pleiotropy, hitchhiking, etc) may act together to govern the changes in allele frequencies of genetic variants associated with complex traits., Highlights • Natural selection on variants affecting complex traits is a common phenomenon. • Natural selection for polygenic traits varies both temporarily and geographically. • Changes in allele frequencies as a result of selection can be highly stochastic. • Multiple selection mechanisms act together on variants affecting complex traits.

Published
2013

10. Parturition

Author

Sam Mesiano, Emily DeFranco, and Louis J. Muglia

Subjects
Pregnancy, Comparative physiology, Cervical dilation, Decidua, Uterus, Myometrium, Physiology, Biology, medicine.disease, Uterine contraction, medicine.anatomical_structure, medicine, Gestation, medicine.symptom
Abstract

The success of pregnancy depends on the appropriate process and timing of parturition. For each viviparous species, natural selection has affected extant physiology such that birth processes and timing complement overall reproductive strategy to maximize reproductive efficiency. This chapter synthesizes the current understanding of the physiology and pathophysiology of human parturition from the perspective of the evolutionary biology and comparative physiology of birth timing. We examine selective pressures that may have influenced parturition physiology and pathophysiology; the principal organ for parturition, the uterus, and its functional tissue types: the myometrium, cervix, and decidua; and the hormonal interactions that control their function to either sustain pregnancy or facilitate labor and delivery. Conserved uterotropic (causing uterine growth) and uterotonic (causing uterine contraction) hormonal pathways are present across viviparous species, although their regulatory patterns and sites of production differ. An emerging theme is that parturition involves positive-feedback loops leading to intrauterine inflammation, enhanced uterine contractility, membrane rupture, and cervical dilation, functioning at a paracrine level within each of the gestational tissues and in an endocrine fashion between the uterus and extrauterine sites.

Published
2015
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11. Contributors

Author

Kjersti M. Aagaard, David F. Albertini, Eugene D. Albrecht, Steven M. Anderson, William E. Armstrong, Richard J. Auchus, Susan P. Bagby, Jacques Balthazart, April K. Binder, Jeffrey D. Blaustein, S. Marc Breedlove, Paula J. Brunton, Jeeyeon Cha, Shawn L. Chavez, Paula E. Cohen, Gerard S. Conway, John F. Couse, Geert J. de Vries, Emily DeFranco, Francesco J. DeMayo, Sudhansu K. Dey, Juan M. Dominguez, Edward M. Eddy, Rafael A. Fissore, Loretta M. Flanagan-Cato, Harvey M. Florman, Nancy G. Forger, Douglas L. Foster, Stephen Franks, Jennifer R. Gardiner, Kathrin Gassei, George D. Giraud, Robert L. Goodman, Andrea C. Gore, David R. Grattan, Janet E. Hall, Kate Hardy, Frances J. Hayes, David Hazlerigg, Mark P. Hedger, Jon D. Hennebold, Allan E. Herbison, Sylvia C. Hewitt, Stanley M. Hileman, Barry T. Hinton, J. Kim Holloway, Elaine M. Hull, Joan S. Hunt, Mary Hunzicker-Dunn, E. Keith Inskeep, Thomas Jansson, Sherri L. Jones, Kenneth S. Korach, Michael J. Large, Jon E. Levine, Xiao-Feng Li, Hyunjung (Jade) Lim, Mark Lindgren, Zhilin Liu, Joseph S. Lonstein, Paul S. MacLean, Catherine A. Marler, Kelly Mayo, Erik C. Mazur, Craig A. McArdle, Margaret M. McCarthy, Neil J. McKenna, James L. McManaman, Sam Mesiano, Joan I. Morrell, Louis J. Muglia, Makoto C. Nagano, Margaret C. Neville, Kevin T. O’Byrne, Peter O’Shaughnessy, Kyle E. Orwig, Stephanie A. Pangas, Gerald J. Pepe, Mariana Pereira, Margaret G. Petroff, James G. Pfaus, Bart T. Phillips, Tony M. Plant, Vincent Prevot, Gail S. Prins, Aleksandar Rajkovic, Cyril Ramathal, Renee A. Reijo Pera, JoAnne S. Richards, Emilie F. Rissman, Bernard Robaire, Mark S. Roberson, Sarah A. Robertson, John A. Russell, Yoel Sadovsky, Masayuki Shimada, Valerie Simonneaux, Lee B. Smith, Richard L. Stouffer, Susan S. Suarez, Melissa A. Suter, Amanda Swain, Manuel Tena-Sempere, Ei Terasawa, Kent L. Thornburg, Paul Le Tissier, Kiyotaka Toshimori, Hanna Valli, William H. Walker, Wipawee Winuthayanon, Selma Feldman Witchel, Larry J. Young, and Anthony J. Zeleznik

Published
2015
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12. Ethanol-Induced Caspase-3 Activation in the in Vivo Developing Mouse Brain

Author

Cleta D'Sa, Louis J. Muglia, John W. Olney, Krikor Dikranian, Kevin A. Roth, Walter J. Jermakowicz, and Tatyana Tenkova

Subjects
Silver Staining, Blotting, Western, Caspase 3, Apoptosis, Neurotransmission, Biology, Sodium Chloride, Sensitivity and Specificity, lcsh:RC321-571, Mice, In vivo, medicine, Animals, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Neurons, TUNEL assay, Ethanol, Neurodegeneration, Glutamate receptor, Brain, Central Nervous System Depressants, medicine.disease, Cell biology, Enzyme Activation, Mice, Inbred C57BL, Neurology, Caspases, NMDA receptor
Abstract

Recently several methods have been described for triggering extensive apoptotic neurodegeneration in the developing in vivo mammalian brain. These methods include treatment with drugs that block NMDA glutamate receptors, drugs that promote GABA(A) neurotransmission, or treatment with ethanol, which has both NMDA antagonist and GABAmimetic properties. A single intoxication episode induced by any of these agents is sufficient to cause widespread neurodegeneration throughout many brain regions. The cell death process transpires rapidly from early to late stages within several hours. As the neurons die, they become TUNEL positive and show, by both light and electron microscopy, all of the classical morphological characteristics of apoptosis. In the present study, using immunocytochemical methods, we document that ethanol intoxication of 7-day-old infant mice causes a widespread pattern of caspase-3 activation corresponding to the pattern of apoptotic neurodegeneration that is occurring simultaneously.

Published
2002

13. Contributors

Author

Philippe F. Backeljauw, Tadej Battelino, Carolyn A. Bondy, Donald Walt Chandler, Dennis J. Chia, Kelly Y. Chun, Pinchas Cohen, David W. Cooke, Sarah C. Couch, Stephen R. Daniels, Mehul Tulsidas Dattani, Diva D. De Leo´n, Johnny Deladoëy, Frank B. Diamond, Leo Dunkel, Christa E. Flück, Michael J. Haller, Bassil Kublaoui, David R. Langdon, Peter A. Lee, Michael A. Levine, Robert H. Lustig, Joseph A. Majzoub, Ram K. Menon, Walter L. Miller, Louis J. Muglia, Jon Nakamoto, Mark R. Palmert, Samuel H. Pepkowitz, Moshe Phillip, Sally Radovick, Robert Rapaport, Scott A. Rivkees, Allen W. Root, Ron G. Rosenfeld, Robert L. Rosenfield, Paul Saenger, Desmond A. Schatz, Mark A. Sperling, Abhinash Srivatsa, Charles A. Stanley, Constantine A. Stratakis, William V. Tamborlane, Paul S. Thornton, Massimo Trucco, Guy Van Vliet, Steven G. Waguespack, Stuart A. Weinzimer, Ram Weiss, William E. Winter, Selma Feldman Witchel, and Anita K. Ying

Published
2014
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15. A solution pathway for preterm birth: accelerating a priority research agenda

Author

Jeffrey C. Murray, Cyril Engmann, Craig E. Rubens, Robert L. Goldenberg, Eve M. Lackritz, Christopher B. Wilson, Catherine Y. Spong, Alan E. Guttmacher, Elizabeth Mason, Joe Leigh Simpson, Jennifer L. Howse, Louis J. Muglia, and Michael G. Gravett

Subjects
Pregnancy, medicine.medical_specialty, Obstetrics, business.industry, Research, lcsh:Public aspects of medicine, MEDLINE, Infant, lcsh:RA1-1270, General Medicine, medicine.disease, Global Health, Infant mortality, Article, Family medicine, Infant Mortality, medicine, Global health, Humans, Premature Birth, Female, business
Published
2013

16. Contributors

Author

John C. Achermann, Steven D. Chernausek, Pinchas Cohen, David W. Cooke, Sarah C. Couch, Steven Daniels, Diva D. De León, Frank B. Diamond, Charis Eng, Delbert A. Fisher, Christa E. Flück, Russel Grant, Annette Grueters, Michael J. Haller, Ieuan A. Hughes, Sharon J. Hyman, David R. Langdon, Peter A. Lee, Robert H. Lustig, Joseph A. Majzoub, Ram K. Menon, Walter L. Miller, Louis J. Muglia, Sally Radovick, Robert Rapaport, Alan M. Rice, Scott A. Rivkees, Allen W. Root, Ron G. Rosenfeld, Robert L. Rosenfield, Paul Saenger, Desmond A. Schatz, Mark A. Sperling, Charles A. Stanley, Mark Stene, Constantine A. Stratakis, William V. Tamborlane, Massimo Trucco, Stuart A. Weinzimer, Ram Weiss, William E. Winter, and Selma Feldman Witchel

Published
2008
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18. Contributors

Author

Ira Adams-Chapman, Anne M. Ades, Amina Ahmed, Simone Albers, Marilee C. Allen, Maureen Andrew, Stephen A. Back, H. Scott Baldwin, Philip L. Ballard, Roberta A. Ballard, Beverly A. Banks-Randall, Stephen Baumgart, Karen P. Beckerman, Thomas J. Benedetti, Gerard T. Berry, Carol Lynn Berseth, Kathleen E. Bethin, Diana W. Bianchi, Mitchell S. Cairo, Anthony Caldamone, Sudhish Chandra, Ramen Chmait, Ronald I. Clyman, Bernard A. Cohen, Meryl S. Cohen, Mitchell I. Cohen, Robert M. Cohn, F. Sessions Cole, Anthony Corbet, Scott C. Denne, Theresa J. Di Maggio, Eric C. Eichenwald, Jacquelyn R. Evans, Nick Evans, Avroy A. Fanaroff, Donna M. Ferriero, Delbert A. Fisher, Laura Flores-Sarnat, Philippe S. Friedlich, J. William Gaynor, Alfred L. Gest, Tal Geva, Mary Ann E. Gibbons, William M. Gilbert, Bertil E. Glader, Christine A. Gleason, Michael J. Goldberg, William V. Good, Gregory Goodwin, Sameer Gopalani, Carol L. Greene, Brian E. Grottkau, Peter J. Gruber, Jean-Pierre Guignard, Susan Guttentag, Shannon E.G. Hamrick, Thomas N. Hansen, Margaret K. Hostetter, Samuel C. Hughes, Andrew D. Hull, Roy Jedeikin, Sandra E. Juul, Bernard S. Kaplan, Paige Kaplan, Rebecca A. Kazin, Thomas F. Kelly, Stefan Kuhle, Ian A. Laing, Harvey L. Levy, Mignon L. Loh, Scott A. Lorch, Ralph A. Lugo, Geoffrey A. Machin, James R. MacMahon, George A. Macones, Ashima Madan, Bradley S. Marino, Alma Martinez, Kathryn L. Maschoff, Patricia Massicotte, Katherine K. Matthay, William C. Mentzer, Jeffrey D. Merrill, Carol A. Miller, Lesley Mitchell, Alicia A. Moise, Thomas J. Mollen, Timothy P. Monahan, Thomas R. Moore, Louis J. Muglia, Robert M. Nelson, Thomas B. Newman, Eugenia K. Pallotto, Erica S. Pan, Elvira Parravicini, J. Colin Partridge, Dan Poenaru, Brenda B. Poindexter, Richard A. Polin, Daniel H. Polk, DeWayne M. Pursley, Rangasamy Ramanathan, Daniela Ramierez-Schrempp, Joan A. Regan, Elisabeth G. Richard, Richard L. Robertson, Mark A. Rosen, Lewis P. Rubin, Jack Rychik, Sulagna C. Saitta, Pablo J. Sánchez, Harvey B. Sarnat, Richard J. Schanler, Mark S. Scher, Istvan Seri, Elaine C. Siegfried, Gary A. Silverman, Rebecca Simmons, Susan Sniderman, Thomas L. Spray, Charles A. Stanley, David K. Stevenson, Barbara J. Stoll, H. William Taeusch, Peter Tarczy-Hornoch, George A. Taylor, Janet A. Thomas, Tivadar Tulassay, Carmella van de Ven, Betty R. Vohr, Robert M. Ward, Peggy Sue Weintrub, Stephen Welty, Gil Wernovsky, Calvin B. Williams, Linda L. Wright, Alison Z. Young, Elaine H. Zackai, and Stephen A. Zderic

Published
2005
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19. Disorders of the Adrenal Gland

Author

Louis J. Muglia and Kathleen E. Bethin

Subjects
medicine.medical_specialty, medicine.anatomical_structure, Endocrinology, Adrenal gland, business.industry, Internal medicine, medicine, business
Published
2005
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