Astrocytes: a Driving Force in Brain Signaling and Encephalopathies Aleksandar Jeremic Iowa State University
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System Inflammation Macrophages/Microglia in Central Nervous Brain Dendritic Cells
Brain Dendritic Cells and Macrophages/Microglia in Central Nervous System Inflammation This information is current as Hans-Georg Fischer and Gaby Reichmann of September 25, 2021. J Immunol 2001; 166:2717-2726; ; doi: 10.4049/jimmunol.166.4.2717 http://www.jimmunol.org/content/166/4/2717 Downloaded from References This article cites 51 articles, 28 of which you can access for free at: http://www.jimmunol.org/content/166/4/2717.full#ref-list-1 Why The JI? Submit online. http://www.jimmunol.org/ • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average by guest on September 25, 2021 Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2001 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Brain Dendritic Cells and Macrophages/Microglia in Central Nervous System Inflammation1 Hans-Georg Fischer2 and Gaby Reichmann Microglia subpopulations were studied in mouse experimental autoimmune encephalomyelitis and toxoplasmic encephalitis. CNS .inflammation was associated with the proliferation of CD11b؉ brain cells that exhibited the dendritic cell (DC) marker CD11c These cells constituted up to 30% of the total CD11b؉ brain cell population. -
Small Molecule Modulators Reveal Mechanisms Regulating Cell Death
Investigating neurodegenerative diseases with small molecule modulators Reka Rebecca Letso Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Graduate School of Arts and Sciences COLUMBIA UNIVERSITY 2011 ©2011 Reka Rebecca Letso All Rights Reserved Abstract Investigating neurodegenerative diseases with small molecule modulators Reka Rebecca Letso Elucidation of the mechanisms underlying cell death in neurodegenerative diseases has proven difficult, due to the complex and interconnected architecture of the nervous system as well as the often pleiotropic nature of these diseases. Cell culture models of neurodegenerative diseases, although seldom recapitulating all aspects of the disease phenotype, enable investigation of specific aspects of these disease states. Small molecule screening in these cell culture models is a powerful method for identifying novel small molecule modulators of these disease phenotypes. Mechanistic studies of these modulators can reveal vital insights into the cellular pathways altered in these disease states, identifying new mechanisms leading to cellular dysfunction, as well as novel therapeutic targets to combat these destructive diseases. Small molecule modulators of protein activity have proven invaluable in the study of protein function and regulation. While inhibitors of protein activity are relatively common, small molecules that can increase protein abundance are quite rare. Small molecule protein upregulators with targeted activities would be of great value in the study of the mechanisms underlying many loss of function diseases. We developed a high- throughput screening approach to identify small molecule upregulators of the Survival of Motor Neuron protein (SMN), whose decreased levels cause the neurodegenerative disease Spinal Muscular Atrophy (SMA). We screened 69,189 compounds for SMN upregulators and performed mechanistic studies on the most active compound, a bromobenzophenone analog designated cuspin-1. -
Mixed Electrical–Chemical Synapses in Adult Rat Hippocampus Are Primarily Glutamatergic and Coupled by Connexin-36
ORIGINAL RESEARCH ARTICLE published: 15 May 2012 NEUROANATOMY doi: 10.3389/fnana.2012.00013 Mixed electrical–chemical synapses in adult rat hippocampus are primarily glutamatergic and coupled by connexin-36 Farid Hamzei-Sichani 1,2,3‡, Kimberly G. V. Davidson4‡,ThomasYasumura4,William G. M. Janssen3, Susan L.Wearne 4#, Patrick R. Hof 3, Roger D.Traub 5†, Rafael Gutiérrez 6, Ole P.Ottersen7 and John E. Rash4,8* 1 Department of Neurosurgery, Mount Sinai School of Medicine, New York, NY, USA 2 Program in Neural and Behavioral Science, Downstate Medical Center, State University of New York, Brooklyn, NY, USA 3 Fishberg Department of Neuroscience, Friedman Brain Institute, Mount Sinai School of Medicine, New York, NY, USA 4 Department of Biomedical Sciences, Colorado State University, Fort Collins, CO, USA 5 Department of Physiology and Pharmacology, Downstate Medical Center, State University of New York, Brooklyn, NY, USA 6 Department of Pharmacobiology, Centro de Investigación y Estudios Avanzados del Instituto Politécnico Nacional, México D.F. 7 Centre for Molecular Biology and Neuroscience, University of Oslo, Oslo, Norway 8 Program in Molecular, Cellular, and Integrative Neurosciences, Colorado State University, Fort Collins, CO, USA Edited by: Dendrodendritic electrical signaling via gap junctions is now an accepted feature of neu- Ryuichi Shigemoto, National Institute ronal communication in mammalian brain, whereas axodendritic and axosomatic gap junc- for Physiological Sciences, Japan tions have rarely been described. We present ultrastructural, immunocytochemical, and Reviewed by: Javier DeFelipe, Cajal Institute, Spain dye-coupling evidence for “mixed” (electrical/chemical) synapses on both principal cells Richard J. Weinberg, University of and interneurons in adult rat hippocampus. -
Deconstructing Spinal Interneurons, One Cell Type at a Time Mariano Ignacio Gabitto
Deconstructing spinal interneurons, one cell type at a time Mariano Ignacio Gabitto Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy under the Executive Committee of the Graduate School of Arts and Sciences COLUMBIA UNIVERSITY 2016 © 2016 Mariano Ignacio Gabitto All rights reserved ABSTRACT Deconstructing spinal interneurons, one cell type at a time Mariano Ignacio Gabitto Abstract Documenting the extent of cellular diversity is a critical step in defining the functional organization of the nervous system. In this context, we sought to develop statistical methods capable of revealing underlying cellular diversity given incomplete data sampling - a common problem in biological systems, where complete descriptions of cellular characteristics are rarely available. We devised a sparse Bayesian framework that infers cell type diversity from partial or incomplete transcription factor expression data. This framework appropriately handles estimation uncertainty, can incorporate multiple cellular characteristics, and can be used to optimize experimental design. We applied this framework to characterize a cardinal inhibitory population in the spinal cord. Animals generate movement by engaging spinal circuits that direct precise sequences of muscle contraction, but the identity and organizational logic of local interneurons that lie at the core of these circuits remain unresolved. By using our Sparse Bayesian approach, we showed that V1 interneurons, a major inhibitory population that controls motor output, fractionate into diverse subsets on the basis of the expression of nineteen transcription factors. Transcriptionally defined subsets exhibit highly structured spatial distributions with mediolateral and dorsoventral positional biases. These distinctions in settling position are largely predictive of patterns of input from sensory and motor neurons, arguing that settling position is a determinant of inhibitory microcircuit organization. -
Protein Kinase C Activates an H' (Equivalent) Conductance in The
Proc. Nati. Acad. Sci. USA Vol. 88, pp. 10816-10820, December 1991 Cell Biology Protein kinase C activates an H' (equivalent) conductance in the plasma membrane of human neutrophils (HI channels/pH regulation/leukocytes/H+-ATPase/bafllomycin) ARVIND NANDA AND SERGIO GRINSTEIN* Division of Cell Biology, Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada Communicated by Edward A. Adelberg, August 12, 1991 ABSTRACT The rate of metabolic acid generation by it can be calculated that pH1 would be expected to drop by neutrophils increases greatly when they are activated. Intra- over 5 units (to pH 1.6) if the metabolically generated H+ cellular acidification is prevented in part by Na+/H' ex- were to remain within the cell. However, cells stimulated in change, but a sizable component ofH+ extrusion persists in the the nominal absence of Na+ and HCO- maintain their pH1 nominal absence of Na' and HCO3 . In this report we deter- above 6.4, suggesting that alternative (Na+- and HCO3- mined the contribution to H+ extrusion of a putative HI independent) H+ extrusion mechanisms must exist in acti- conductive pathway and its mode ofactivation. In unstimulated vated neutrophils. Accordingly, accelerated extracellular cells, H+ conductance was found to be low and unaffected by acidification can be recorded under these conditions. depolarization. An experimental system was designed to min- The existence of H+-conducting channels has been docu- imize the metabolic acid generation and membrane potential mented in snail neurones (5) and axolotl oocytes (6). In these changes associated with neutrophil activation. By using this tissues, the channels are inactive at the resting plasma system, (3-phorbol esters were shown to increase the H+ membrane potential (Em) but open when the membrane (equivalent) permeability of the plasma membrane. -
Autophagy Flux in Critical Illness, a Translational Approach
www.nature.com/scientificreports OPEN Autophagy fux in critical illness, a translational approach Nicolas Tardif 1,2, Franck Polia2, Inga Tjäder1,2, Thomas Gustafsson3 & Olav Rooyackers1,2 Recent clinical trials suggest that early nutritional support might block the induction of autophagy in Received: 17 October 2018 critically ill patients leading to the development of organ failure. However, the regulation of autophagy, Accepted: 7 June 2019 especially by nutrients, in critical illness is largely unclear. The autophagy fux (AF) in relation to critical Published: xx xx xxxx illness and nutrition was investigated by using an in vitro model of human primary myotubes incubated with serum from critically ill patients (ICU). AF was calculated as the diference of p62 expression in the presence and absence of chloroquine (50 µM, 6 h), in primary myotubes incubated for 24 h with serum from healthy volunteers (n = 10) and ICU patients (n = 93). We observed 3 diferent phenotypes in AF, non-altered (ICU non-responder group), increased (ICU inducer group) or blocked (ICU blocker group). This block was not associate with a change in amino acids serum levels and was located at the accumulation of autophagosomes. The increase in the AF was associated with lower serum levels of non-essential amino acids. Thus, early nutrition during critical illness might not block autophagy but could attenuate the benefcial efect of starvation on reactivation of the autophagy process. This could be of clinical importance in the individual patients in whom this process is inhibited by the critical illness insult. Critically ill patients treated in an Intensive Care Unit (ICU) ofen have organ failure already at their admittance or will develop it early during their stay in the unit. -
Gabaergic Signaling Linked to Autophagy Enhances Host Protection Against Intracellular Bacterial Infections
ARTICLE DOI: 10.1038/s41467-018-06487-5 OPEN GABAergic signaling linked to autophagy enhances host protection against intracellular bacterial infections Jin Kyung Kim1,2,3, Yi Sak Kim1,2,3, Hye-Mi Lee1,3, Hyo Sun Jin4, Chiranjivi Neupane 2,5, Sup Kim1,2,3, Sang-Hee Lee6, Jung-Joon Min7, Miwa Sasai8, Jae-Ho Jeong 9,10, Seong-Kyu Choe11, Jin-Man Kim12, Masahiro Yamamoto8, Hyon E. Choy 9,10, Jin Bong Park 2,5 & Eun-Kyeong Jo1,2,3 1234567890():,; Gamma-aminobutyric acid (GABA) is the principal inhibitory neurotransmitter in the brain; however, the roles of GABA in antimicrobial host defenses are largely unknown. Here we demonstrate that GABAergic activation enhances antimicrobial responses against intracel- lular bacterial infection. Intracellular bacterial infection decreases GABA levels in vitro in macrophages and in vivo in sera. Treatment of macrophages with GABA or GABAergic drugs promotes autophagy activation, enhances phagosomal maturation and antimicrobial responses against mycobacterial infection. In macrophages, the GABAergic defense is mediated via macrophage type A GABA receptor (GABAAR), intracellular calcium release, and the GABA type A receptor-associated protein-like 1 (GABARAPL1; an Atg8 homolog). Finally, GABAergic inhibition increases bacterial loads in mice and zebrafish in vivo, sug- gesting that the GABAergic defense plays an essential function in metazoan host defenses. Our study identified a previously unappreciated role for GABAergic signaling in linking antibacterial autophagy to enhance host innate defense against intracellular bacterial infection. 1 Department of Microbiology, Chungnam National University School of Medicine, Daejeon 35015, Korea. 2 Department of Medical Science, Chungnam National University School of Medicine, Daejeon 35015, Korea. -
Canine Dorsal Root Ganglia Satellite Glial Cells Represent an Exceptional Cell Population with Astrocytic and Oligodendrocytic P
www.nature.com/scientificreports OPEN Canine dorsal root ganglia satellite glial cells represent an exceptional cell population with astrocytic and Received: 17 August 2017 Accepted: 6 October 2017 oligodendrocytic properties Published: xx xx xxxx W. Tongtako1,2, A. Lehmbecker1, Y. Wang1,2, K. Hahn1,2, W. Baumgärtner1,2 & I. Gerhauser 1 Dogs can be used as a translational animal model to close the gap between basic discoveries in rodents and clinical trials in humans. The present study compared the species-specifc properties of satellite glial cells (SGCs) of canine and murine dorsal root ganglia (DRG) in situ and in vitro using light microscopy, electron microscopy, and immunostainings. The in situ expression of CNPase, GFAP, and glutamine synthetase (GS) has also been investigated in simian SGCs. In situ, most canine SGCs (>80%) expressed the neural progenitor cell markers nestin and Sox2. CNPase and GFAP were found in most canine and simian but not murine SGCs. GS was detected in 94% of simian and 71% of murine SGCs, whereas only 44% of canine SGCs expressed GS. In vitro, most canine (>84%) and murine (>96%) SGCs expressed CNPase, whereas GFAP expression was diferentially afected by culture conditions and varied between 10% and 40%. However, GFAP expression was induced by bone morphogenetic protein 4 in SGCs of both species. Interestingly, canine SGCs also stimulated neurite formation of DRG neurons. These fndings indicate that SGCs represent an exceptional, intermediate glial cell population with phenotypical characteristics of oligodendrocytes and astrocytes and might possess intrinsic regenerative capabilities in vivo. Since the discovery of glial cells over a century ago, substantial progress has been made in understanding the origin, development, and function of the diferent types of glial cells in the central nervous system (CNS) and peripheral nervous system (PNS)1. -
Comparative Morphology of Gigantopyramidal Neurons in Primary Motor Cortex Across Mammals
Received: 23 August 2017 | Revised: 19 October 2017 | Accepted: 24 October 2017 DOI: 10.1002/cne.24349 The Journal of RESEARCH ARTICLE Comparative Neurology Comparative morphology of gigantopyramidal neurons in primary motor cortex across mammals Bob Jacobs1 | Madeleine E. Garcia1 | Noah B. Shea-Shumsky1 | Mackenzie E. Tennison1 | Matthew Schall1 | Mark S. Saviano1 | Tia A. Tummino1 | Anthony J. Bull2 | Lori L. Driscoll1 | Mary Ann Raghanti3 | Albert H. Lewandowski4 | Bridget Wicinski5 | Hong Ki Chui1 | Mads F. Bertelsen6 | Timothy Walsh7 | Adhil Bhagwandin8 | Muhammad A. Spocter8,9,10 | Patrick R. Hof5 | Chet C. Sherwood11 | Paul R. Manger8 1Laboratory of Quantitative Neuromorphology, Neuroscience Program, Colorado College, Colorado Springs, Colorado 2Human Biology and Kinesiology, Colorado College, Colorado Springs, Colorado 3Department of Anthropology and School of Biomedical Sciences, Kent State University, Kent, Ohio 4Cleveland Metroparks Zoo, Cleveland, Ohio 5Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 6Center for Zoo and Wild Animal Health, Copenhagen Zoo, Fredericksberg, Denmark 7Smithsonian National Zoological Park, Washington, District of Columbia 8School of Anatomical Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa 9Department of Anatomy, Des Moines University, Des Moines, Iowa 10Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, Iowa 11Department of Anthropology and Center for the Advanced Study of Human Paleobiology, The George Washington University, Washington, District of Columbia Correspondence Bob Jacobs, Ph.D., Laboratory of Abstract Quantitative Neuromorphology, Gigantopyramidal neurons, referred to as Betz cells in primates, are characterized by large somata Neuroscience Program, Colorado College, and extensive basilar dendrites. Although there have been morphological descriptions and draw- 14 E. -
A Single-Neuron: Current Trends and Future Prospects
cells Review A Single-Neuron: Current Trends and Future Prospects Pallavi Gupta 1, Nandhini Balasubramaniam 1, Hwan-You Chang 2, Fan-Gang Tseng 3 and Tuhin Subhra Santra 1,* 1 Department of Engineering Design, Indian Institute of Technology Madras, Tamil Nadu 600036, India; [email protected] (P.G.); [email protected] (N.B.) 2 Department of Medical Science, National Tsing Hua University, Hsinchu 30013, Taiwan; [email protected] 3 Department of Engineering and System Science, National Tsing Hua University, Hsinchu 30013, Taiwan; [email protected] * Correspondence: [email protected] or [email protected]; Tel.: +91-044-2257-4747 Received: 29 April 2020; Accepted: 19 June 2020; Published: 23 June 2020 Abstract: The brain is an intricate network with complex organizational principles facilitating a concerted communication between single-neurons, distinct neuron populations, and remote brain areas. The communication, technically referred to as connectivity, between single-neurons, is the center of many investigations aimed at elucidating pathophysiology, anatomical differences, and structural and functional features. In comparison with bulk analysis, single-neuron analysis can provide precise information about neurons or even sub-neuron level electrophysiology, anatomical differences, pathophysiology, structural and functional features, in addition to their communications with other neurons, and can promote essential information to understand the brain and its activity. This review highlights various single-neuron models and their behaviors, followed by different analysis methods. Again, to elucidate cellular dynamics in terms of electrophysiology at the single-neuron level, we emphasize in detail the role of single-neuron mapping and electrophysiological recording. We also elaborate on the recent development of single-neuron isolation, manipulation, and therapeutic progress using advanced micro/nanofluidic devices, as well as microinjection, electroporation, microelectrode array, optical transfection, optogenetic techniques. -
Cisplatin-Induced Apoptosis Inhibits Autophagy, Which Acts As a Pro-Survival Mechanism in Human Melanoma Cells
Cisplatin-Induced Apoptosis Inhibits Autophagy, Which Acts as a Pro-Survival Mechanism in Human Melanoma Cells Barbara Del Bello, Marzia Toscano, Daniele Moretti, Emilia Maellaro* Department of Pathophysiology, Experimental Medicine and Public Health, Istituto Toscano Tumori, University of Siena, Siena, Italy Abstract The interplay between a non-lethal autophagic response and apoptotic cell death is still a matter of debate in cancer cell biology. In the present study performed on human melanoma cells, we investigate the role of basal or stimulated autophagy in cisplatin-induced cytotoxicity, as well as the contribution of cisplatin-induced activation of caspases 3/7 and conventional calpains. The results show that, while down-regulating Beclin-1, Atg14 and LC3-II, cisplatin treatment inhibits the basal autophagic response, impairing a physiological pro-survival response. Consistently, exogenously stimulated autophagy, obtained with trehalose or calpains inhibitors (MDL-28170 and calpeptin), protects from cisplatin-induced apoptosis, and such a protection is reverted by inhibiting autophagy with 3-methyladenine or ATG5 silencing. In addition, during trehalose-stimulated autophagy, the cisplatin-induced activation of calpains is abrogated, suggesting the existence of a feedback loop between the autophagic process and calpains. On the whole, our results demonstrate that in human melanoma cells autophagy may function as a beneficial stress response, hindered by cisplatin-induced death mechanisms. In a therapeutic perspective, these findings suggest that the efficacy of cisplatin-based polychemotherapies for melanoma could be potentiated by inhibitors of autophagy. Citation: Del Bello B, Toscano M, Moretti D, Maellaro E (2013) Cisplatin-Induced Apoptosis Inhibits Autophagy, Which Acts as a Pro-Survival Mechanism in Human Melanoma Cells. -
Selective Gene Expression in Brain Microglia Mediated Via Adeno-Associated Virus Type 2 and Type 5 Vectors
Gene Therapy (2003) 10, 657–667 & 2003 Nature Publishing Group All rights reserved 0969-7128/03 $25.00 www.nature.com/gt RESEARCH ARTICLE Selective gene expression in brain microglia mediated via adeno-associated virus type 2 and type 5 vectors M Cucchiarini1,w, XL Ren1, G Perides2 and EF Terwilliger1 1Division of Experimental Medicine, Harvard Institutes of Medicine and Beth Israel Deaconess Medical Center, Boston, MA, USA; and 2Department of Surgery, Beth Israel Deaconess Medical Center, and Harvard Medical School, Boston, MA, USA Microglia represent a crucial cell population in the central examined, an element derived from the gene for the murine nervous system, participating in the regulation and surveil- macrophage marker F4/80 was the most discriminating for lance of physiological processes as well as playing key roles microglia. Gene expression from vectors controlled by this in the etiologies of several major brain disorders. The ability element was highly selective for microglia, both in vitro and in to target gene transfer vehicles selectively to microglia would vivo. To our knowledge, this is the first demonstration of provide a powerful new approach to investigations of selective expression of transferred genes in microglia using mechanisms regulating brain pathologies, as well as enable AAV-derived vectors, as well as the first utilization of the development of novel therapeutic strategies. In this recombinant AAV-5 vectors in any macrophage lineage. study, we evaluate the feasibility of specifically and efficiently These results provide strong encouragement for the applica- targeting microglia relative to other brain cells, using vectors tion of these vectors and this approach for delivering based on two different serotypes of adeno-associated virus therapeutic and other genes selectively to microglia.