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Cognitive deficits and their underlying structural and functional alterations in mice selectively bred for high stress reactivity [Elektronische Ressource] / Alana Knapman

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Cognitive Deficits and their Underlying Structural and Functional Alterations in Mice Selectively Bred for High Stress Reactivity Alana Knapman Dissertation Faculty of Biology Ludwig Maximilian University, Munich Cognitive Deficits and their Underlying Structural and Functional Alterations in Mice Selectively Bred for High Stress Reactivity Dissertation Faculty of Biology Ludwig Maximilian University Munich Alana Knapman Msc rdborn 23 June 1979 in Landvetter, Sweden Munich, 2010 Supervisor: Dr. Chadi Touma 1. Examiner: Prof. Dr. Rainer Landgraf 2. Examiner: Prof. Dr. Lutz Wiegrebe Examination date: 14.12.2010 “Intellect is in itself a mode of exaggeration, and destroys the harmony of any face.” Oscar Wilde Content 5 CONTENT CONTENT 5 ABBREVIATIONS 7 LIST OF PUBLICATIONS 10 SUMARY 1 AIMS OF THE THESIS 13 INTRODUCTION 14 MAJOR DEPRESSION…………………………………………………………...14 Symptoms of Major Depression………………………………………………..14 Subtypes of Major Depression…………………………………………………15 Treatment of Major Depression………………………………………………..16 SCHIZOPHRENIA……………………………………………...………………….16 Symptoms of Schizophrenia……………………………………………………17 Treatment of Schizophrenia…………………………………………………….17 SIMILARITIES BETWEEN MAJOR DEPRESSION AND SCHIZOPHRENIA…………………………………………………………..

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Published 01 January 2010
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Cognitive Deficits and their Underlying Structural and Functional Alterations in Mice Selectively Bred for High Stress Reactivity
Alana Knapman
Dissertation Faculty of Biology Ludwig Maximilian University, Munich
Cognitive Deficits and their Underlying Structural and Functional Alterations in Mice Selectively Bred for High Stress Reactivity Dissertation Faculty of Biology Ludwig Maximilian University Munich Alana Knapman Msc rd born 23 June 1979 in Landvetter, Sweden Munich, 2010
Supervisor: Dr. Chadi Touma 1. Examiner: Prof. Dr. Rainer Landgraf 2. Examiner: Prof. Dr. Lutz Wiegrebe Examination date: 14.12.2010
“Intellect is in itself a mode of exaggeration, and destroys the harmony of any face.” Oscar Wilde
Content 5CONTENT CONTENT 5 ABBREVIATIONS 7 LIST OF PUBLICATIONS 10 SUMMARY 11 AIMS OF THE THESIS 13 INTRODUCTION 14 MAJOR DEPRESSION…………………………………………………………...14 Symptoms of Major Depression………………………………………………..14 Subtypes of Major Depression…………………………………………………15 Treatment of Major Depression………………………………………………..16 SCHIZOPHRENIA……………………………………………...………………….16 Symptoms of Schizophrenia……………………………………………………17 Treatment of Schizophrenia…………………………………………………….17 SIMILARITIES BETWEEN MAJOR DEPRESSION AND SCHIZOPHRENIA…………………………………………………………..17 MODELING PSYCHIATRIC DISEASES IN MICE……………………………..18
THE STRESS REACTIVITY MOUSE MODEL…………………………………29
AIMS AND SCOPE OF THE THESIS…………………………………………...20
DISCUSSION 23
A GENETIC PREDISPOSTION FOR INCREASED STRESS REACTIVITY……………………………………………………………23
COGNITIVE DEFICITS IN PSYCHIATRIC DISORDERS…………………….24
THE EFFECT OF EXCESS GLUCOCORTICOID EXPOSURE ON THE HIPPOCAMPUS…………………………………………………………………...25
Content 6GLUCOCORTICOID EXPOSURE AND NEURONAL DEATH……………….25
MITOCHONDRIAL DYSFUNCTION IN PSYCHIATRIC DISORDERS……...26
THE NEUROTROPHIC HYPOTHESIS OF MAJOR DEPRESSION…..…….27
THE ASSOCIATION BETWEEEN ENERGY METABOLISM, BRAIN-DERIVED NEUROTROPHIC FACTOR AND N-ACETYLASPARTATE LEVELS……………………………………………………………………………..28
ADVANTAGES OF THE STRESS REACTIVITY MODEL…………..………..29
OUTLOOK AND CONCLUDING REMARKS………..............................…….29
REFERENCES 31
ACKNOWLEDGEMENTS 40
DECLARATION 42
DECLARATION OF CONTRIBUTION AS CO-AUTHOR 43
CURRICULUM VITAE 44
PAPER I
PAPER II
PAPER III
Abbreviations
ABBREVIATIONS 2-DE Two-dimensional gel electrophoresis ANOVA One factor analysis of variance ATP Adenosine-5'-triphosphate BDNF Brain derived neurotrophic factor CgCtx Cingulate cortex CHESS Chemical shift selective CP Caudate putamen Cre Creatine CRH Corticotrophin releasing hormone CS Conditioned stimulus DAT Dopamine transporter D1R Dopamine 1 receptor D2R Dopamine 2 receptor ELISA Enzyme-linked immunosorbent assay FWHM Full-with-at-half-maximum FST Forced swim test 1 H-MRS Proton magnetic resonance spectroscopy HPA Hypothalamus-pituitary-adrenal HR High stress reactive i.p Intraperitoneally IR Intermediate stress reactive ITI Inter-trial interval KWH-test Kruskall-Wallis H-test Li Latent inhibition LiCl Lithium chloride LTP Long term potentiation
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Abbreviations
LR MALDI MEMRI
MD MnCl2MR MRI MWU-test MS N NAc NAA NAAG NaCl No-PE NOR PFC PE pI/MW ppm RARE ROI RIA SEM S/N SNP SR SRT
Low stress reactive Matrix-assisted laser desorption/ionization Manganese-enhanced magnetic resonance imaging Major Depression Manganse Chloride
Magnetic resonance
Magnetic resonance imaging Mann-Whitney U-test Mass spectrometry Number of animals Nucleus accumbens N-acetylaspartate N-acetyl-aspartylglutamate Sodium chloride Non Pre-exposed
Novel object recognition
Prefrontal cortex
Pre-exposed Isoelectric point/molecular weight Parts per million Relaxation enhanced Region of interest Radioimmunoassay Standard error of the mean Signal to noise ratio Single nucleotide polymorphism Stress reactivity Stress reactivity test
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