Verfügbarkeit: Gene-environment interplay of extreme anxiety-related behavior

Gene-environment interplay of extreme anxiety-related behavior: implications for corticotropin-releasing hormone receptor 1

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Bibliographische Detailangaben
Beteilige Person:	Sotnikov, Sergey (VerfasserIn)
Format:	Hochschulschrift/Dissertation Buch
Sprache:	Englisch
Veröffentlicht:	2013
Schlagwörter:	Hochschulschrift
Links:	https://nbn-resolving.org/urn:nbn:de:bvb:19-171139 http://d-nb.info/1053618662/34 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=027470487&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA
Umfang:	VI, 136 S. Ill., graph. Darst.
Format:	Langzeitarchivierung gewährleistet, LZA

Internformat

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Datensatz im Suchindex

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adam_text	GENE-ENVIRONMENT INTERPLAY OF EXTREME ANXIETY-RELATED BEHAVIOR: IMPLICATIONS FOR CORTICOTROPIN-RELEASING HORMONE RECEPTOR 1 DISSERTATION FAKULTAT FUR BIOLOGIE LUDWIG-MAXIMILIANS-UNIVERSITAT MIINCHEN ANGEFERTIGT AM MAX-PLANCK-INSTITUT FUR PSYCHIATRIE, MTINCHEN M A X-PI.A IVR .K-CKSF.I.I.SCH A FT VORGELEGT VON SERGEY VALERIEVICH SOTNIKOV MTINCHEN, 12. NOVEMBER 2013 HTTP://D-NB.INFO/1054304890 1 5 8 10 10 11 11 12 13 15 19 19 20 .21 23 23 .26 .29 .30 .30 .30 30 TABLE OF CONTENTS TABLE OF CONTENTS LIST OF ABBREVIATIONS ABSTRACT 1 INTRODUCTION 1.1 WHAT IS AN ANXIETY DISORDER? 1.2 GENE-ENVIRONMENT INTERPLAY IN RELATION TO ANXIETY DISORDERS 1.2.1 CONCEPTS OF GENE-ENVIRONMENT INTERPLAY 1.2.2 GENE-ENVIRONMENT INTERPLAY FROM THE PERSPECTIVE OF GENETIC BACKGROUND 1.2.3 GENE-ENVIRONMENT INTERPLAY FROM THE PERSPECTIVE OF ENVIRONMENTAL INFLUENCES 1.3 EPIGENETIC MECHANISM BEHIND GENE-ENVIRONMENT INTERPLAY 1.4 THE ROLE OF THE CRH SYSTEM IN ANXIETY-RELATED BEHAVIOR 1.4.1 CRH: DISCOVERY AND RELATION TO ANXIETY 1.4.2 CRH RECEPTOR 1: IMPLICATION TO ANXIETY DISORDERS AND PHARMACOLOGICAL INTERVENTIONS 1.4.3 CRH RECEPTOR 1 ROLE IN THE AMYGDALE 1.5 MODELING ANXIETY DISORDERS IN MICE 1.5.1 TESTING VALIDITY OF ANXIETY MODELS 1.5.2 THE HAB/LAB MOUSE MODEL 2 AIMS OF THE THESIS 3 MATERIALS AND METHODS 3.1 ANIMALS AND HOUSING CONDITIONS 3.2 BEHAVIORAL PHENOTYPING 3.2.1 TMT-AVOIDANCE TEST 3.2.1.1 AVOIDANCE BEHAVIOR OF CD1 MICE 31 3.2.1.2 AVOIDANCE BEHAVIOR OF HAB/NAB/LAB MICE 31 3.2.2 ELEVATED PLUS-MAZE TEST (EPM) 32 3.2.3 LIGHT-DARK BOX (LDB) 32 3.2.4 HOME CAGE ACTIVITY (HCA) 32 3.2.5 TAIL SUSPENSION TEST (TST) 33 3.2.6 FORCED SWIMMING TEST (FST) 33 3.2.7 SUCROSE PREFERENCE TEST 33 3.3 ANALYSIS OF NEUROENDOCRINOLOGICAL PARAMETERS 34 3.3.1 HPA AXIS REGULATION 34 3.3.2 RADIOIMMUNOASSAY (RIA) 34 3.3.3 BODY AND ORGANS WEIGHT 35 3.4 CHRONIC MILD STRESS PARADIGM 35 3.5 KILLING OF ANIMALS AND BRAIN HARVESTING 35 3.6 C-FOS IN SITU HYBRIDIZATION 35 3.7 RNA EXTRACTION, CDNA PREPARATION AND QUANTITATIVE REAL-TIME PCR 37 3.8 DNA EXTRACTION, BISULFITE CONVERSION AND PYROSEQUENCING 41 3.9 CONSTRUCTION OF PROMOTER-LUCIFERASE REPORTERS 43 3.10 IN VITRO METHYLATION OF DNA AND BISULPHITE SEQUENCING 45 3.11 CELL CULTURE, TRANSFECTION AND REPORTER GENE ASSAY 47 3.12 WESTERN BLOTTING 48 3.13 IMMUNOFLUORESCENT ASSAYS 51 3.14 ELECTROPHORETIC MOBILITY SHIFT ASSAY (EMSA) 51 3.15 CHRONIC VALPROIC ACID (VPA) TREATMENT 54 3.16 STATISTICAL ANALYSIS 54 4 RESULTS 56 4.1 EVALUATION OF THE ANXIETY-RELATED BEHAVIOR USING THETMT-AVOIDANCE TEST.... 56 2 4.1.1 EFFECTS OF TMT, CAT FUR AND BUTYRIC ACID ON AVOIDANCE BEHAVIOR OF CD1 MICE 56 4.1.2 TMT-AVOIDANCE IN HAB/NAB/LAB MICE 58 4.2 EFFECTS OF CMS ON THE PHENOTYPIC CHARACTERISTICS OF LAB MICE 60 4.2.1 CHANGES IN ANXIETY-RELATED BEHAVIOR 60 4.2.2 CHANGES IN DEPRESSION-LIKE BEHAVIOR 64 4.2.3 CHANGES IN NEUROENDOCRINE PARAMETERS 66 4.3 EFFECT OF CMS ON C-FOS EXPRESSION AFTER TMT EXPOSURE 69 4.4 EFFECT OF CMS ON GENE EXPRESSION IN THE BLA 70 4.5 EFFECT OF CMS ON CRHRL DNA METHYLATION IN THE BLA 72 4.6 ROLE OF YY1 IN THE METHYLATION-SENSITIVE REGULATION OF THE CRHRL 76 4.6.1 YY1 EXPRESSION AFTER CMS AND ITS ROLE IN THE REGULATION OF CRHRL PROMOTER 76 4.6.2 SELECTIVE BINDING OF YY1 TO THE RECOGNITION SEQUENCE CLOSE TO CPG1 81 4.6.3 YY1 BINDS TO CRHRL IN A METHYLATION-SENSITIVE MANNER BUT DOES NOT INDUCE INCREASE IN METHYLATION OF CPG1 83 4.7 POSSIBLE EPIGENETIC MECHANISMS CONTRIBUTING TO DIFFERENT BASAL CRHRL EXPRESSION IN THE BLA OF HAB/LAB MICE 85 4.7.1 ABSENCE OF GENETIC VARIABILITY IN CRHRL GENE BETWEEN HAB AND LAB MICE 85 4.7.2 POSSIBLE ROLE OF MIRNA34 FAMILY 86 4.7.3 POSSIBLE ROLE OF HISTONE MODIFICATIONS 87 5 DISCUSSION 91 5.1 TMT AVOIDANCE AS A NOVEL APPROACH TO EVALUATE ANXIETY-RELATED BEHAVIOR 91 5.2 CHRONIC MILD STRESS INCREASED ANXIETY-RELATED AND DEPRESSION-LIKE BEHAVIORS IN LAB MICE 92 3 5.3 TMT EXPOSURE REVEALS A CRITICAL ROLE OF THE BASOLATERAL AMYGDALA FOR THE ANXIETY SHIFT AFTER CMS 94 5.4 CMS INCREASED EXPRESSION OF CRHRL AND SITE-SPECIFIC METHYLATION OF ITS PROMOTER IN THE BLA 96 5.5 BINDING OF THE TRANSCRIPTION FACTOR YY1 ENHANCED CRHRL PROMOTER ACTIVITY IN A METHYLATION-SENSETIVE MANNER 99 5.6 OTHER POSSIBLE EPIGENETIC MECHANISMS CONTRIBUTING TO CRHRL EXPRESSION 102 5.7 SUMMARY AND PERSPECTIVES 106 6 LIST OF REFERENCES 108 7 ACKNOWLEDGMENTS 132 8 CURRICULUM VITAE 134 9 DECLARATION/ERKLARUNG 136 4
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spellingShingle	Sotnikov, Sergey Gene-environment interplay of extreme anxiety-related behavior implications for corticotropin-releasing hormone receptor 1
subject_GND	(DE-588)4113937-9
title	Gene-environment interplay of extreme anxiety-related behavior implications for corticotropin-releasing hormone receptor 1
title_auth	Gene-environment interplay of extreme anxiety-related behavior implications for corticotropin-releasing hormone receptor 1
title_exact_search	Gene-environment interplay of extreme anxiety-related behavior implications for corticotropin-releasing hormone receptor 1
title_full	Gene-environment interplay of extreme anxiety-related behavior implications for corticotropin-releasing hormone receptor 1 Sergey Sotnikov
title_fullStr	Gene-environment interplay of extreme anxiety-related behavior implications for corticotropin-releasing hormone receptor 1 Sergey Sotnikov
title_full_unstemmed	Gene-environment interplay of extreme anxiety-related behavior implications for corticotropin-releasing hormone receptor 1 Sergey Sotnikov
title_short	Gene-environment interplay of extreme anxiety-related behavior
title_sort	gene environment interplay of extreme anxiety related behavior implications for corticotropin releasing hormone receptor 1
title_sub	implications for corticotropin-releasing hormone receptor 1
topic_facet	Hochschulschrift
url	https://nbn-resolving.org/urn:nbn:de:bvb:19-171139 http://d-nb.info/1053618662/34 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=027470487&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA
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