Regulation of neurogenesis in the adult mammalian brain [Elektronische Ressource] / vorgelegt von Christiana Marie Cooper-Kuhn

Sujets

• Biologie

Informations

• Publié par: universitat_regensburg
• Publié le: 01 janvier 2003
• Nombre de lectures: 10
• Langue: English
• Poids de l'ouvrage: 91 Mo

Extrait

REGULATION OF NEUROGENESIS
IN THE ADULT MAMMALIAN BRAIN
DISSERTATION ZUR ERLANGUNG DES DOKTORGRADES DER
NATURWISSENSCHAFTEN (DR. RER. NAT.) DER
NATURWISSENSCHAFTLICHEN FAKULTÄT III - BIOLOGIE UND
VORKLINISCHE MEDIZIN DER UNIVERSITÄT REGENSBURG
vorgelegt von
Christiana Marie Cooper-Kuhn aus Boulder, Colorado USA
2003Promotionsgesuch eingereicht am: 18.02.2003
Die Arbeit wurde angeleitet von: Prof. rer. nat. Stephan Schneuwly und Prof. Dr. med.
Jürgen Winkler in der Klinik und Poliklinik für Neurologie der Universität Regensburg
Prüfungsausschuß: Vorsitzender: - Prof. Dr. Karl Kunzelmann
1. Prüfer (Erstgutachten) – Prof. Dr. Stephan Schneuwly
2. Prüfer (Zweitgutachten) – Prof. Dr. Jürgen Winkler
3. Prüfer – Prof. Dr. Inga Neumann
2It is only when we forget all our learning that we begin to know.” – Thoreau
“If you have built castles in the air, your work need not be lost. That is where they
should be. Now put the foundation under them.” - Thoreau
3INDEX
REGULATION OF NEUROGENESIS IN THE ADULT MAMMALIAN BRAIN................................................1
LIST OF ABBREVIATIONS .................................................................................................................................8
INTRODUCTION.................................................................................................................................................10
GENERATION OF NEW NEURONS IN THE ADULT MAMMALIAN BRAIN .....................................................................10
Subventricular Zone/Olfactory Bulb Neurogenesis ..................................................................................11
Hippocampal Neurogenesis ......................................................................................................................13
DEVELOPMENTAL ASPECTS OF ADULT NEUROGENESIS.....................................................................................15
PHYLOGENETIC AADULT N........................................................................................17
Invertebrates ..............................................................................................................................................17
Non-mammalian vertebrates .....................................................................................................................17
Mammals....................................................................................................................................................18
FUNDAMENTALS OF ADULT NEUROGENESIS ......................................................................................................19
REGULATING ADULT NEUROGENESIS: WHICH STIMULI MAKE A DIFFERENCE?...................................................23
Systemic Influences:..................................................................................................................................23
Extracellular cues:......................................................................................................................................25
OVERALL GOAL................................................................................................................................................27
SPECIFIC AIMS..................................................................................................................................................27
OVERVIEW .........................................................................................................................................................29
EXPERIMENTS...................................................................................................................................................30
EXPERIMENT I - CRITICAL EVALUATION OF BRDU LABELING...............................................................30
OBJECTIVE .......................................................................................................................................................30
INTRODUCTION TO EXPERIMENT........................................................................................................................30
EXPERIMENTAL DESIGN ....................................................................................................................................32
RESULTS AND DISCUSSION ...............................................................................................................................32
SUMMARY.........................................................................................................................................................41
EXPERIMENT II - IMPAIRED ADULT NEUROGENESIS IN MICE LACKING THE TRANSCRIPTION
FACTOR E2F1....................................................................................................................................................42
OBJECTIVE .......................................................................................................................................................42
INTRODUCTION TO EXPERIMENT........................................................................................................................43
EXPERIMENTAL DESIGN ....................................................................................................................................45
RESULTS........................................................................................................................................................45
Loss of E2F1 affects size of adult mice and brain weight........................................................................45
Neuroanatomy of adult E2F1-deficient animals........................................................................................46
4Loss of E2F1 leads to less proliferation in dentate gyrus and subventricular zone................................48
Loss of E2F1 results in significant decrease of neurons in dentate gyrus and olfactory bulb................50
Loss of E2F1 results in decreased cell death in dentate gyrus and olfactory bulb granule cell layers.
....................................................................................................................................................................51
DISCUSSION..................................................................................................................................................53
Functional significance of E2F1 in other animal models..........................................................................53
Cell death in regions of adult neurogenesis..............................................................................................53
Postnatal phenotype of E2F1-deficiency ..................................................................................................54
EXPERIMENTS III & IV - NEUROTRANSMITTERS AND THEIR POSITION IN THE GAME OF ADULT
NEUROGENESIS ...............................................................................................................................................56
EXPERIMENT III – CHOLINERGIC DENERVATION LESION........................................................................57
OBJECTIVE .......................................................................................................................................................57
INTRODUCTION TO EXPERIMENT........................................................................................................................58
EXPERIMENTAL DESIGN ....................................................................................................................................59
RESULTS........................................................................................................................................................60
ICV injections of 192IgG-saporin result in selective elimination of cholinergic neurons in medial
septum........................................................................................................................................................60
Decrease of Neurogenesis in Dentate Gyrus after Cholinergic Denervation..........................................60
Cholinergic Denervation causes increase in Non-neuronal Cells in the Dentate Gyrus ........................62
Cholinergic Denervation causes an increase in Cell Death in the Dentate Gyrus..................................62
Decrease of Neurogenesis in Olfactory Bulb after Cholinergic Denervation ..........................................63
Cholinergic Denervation causes an increase in Cell Death in the Periglomerular Layer.......................65
DISCUSSION..................................................................................................................................................65
EXPERIMENT IV – NORADRENERGIC DENERVATION LESION................................................................68
OBJECTIVE .......................................................................................................................................................68
INTRODUCTION TO EXPERIMENT........................................................................................................................68
EXPERIMENTAL DESIGN ....................................................................................................................................69
RESULTS........................................................................................................................................................69