Parkinson’s disease is a disorder mainly characterized by progressive degeneration of dopamine producing neurons in the substantia nigra of the midbrain. The most commonly used treatment strategy is to pharmacologically restore the lost function by the administration of the dopaminergic precursor L-DOPA. Another treatment strategy is to replace the degenerated neurons with immature fetal ventral mesencephalic tissue, or ultimately stem cell-derived tissue….
Contents
INTRODUCTION
General history and background
The neurotransmitter dopamine
Clinical features and pathology
Etiology
The basal ganglia system
Treatment strategies
Nerve fiber formation
Neurotrophic factors
6-OHDA model of Parkinson’s disease
Animal model of L-DOPA induced dyskinesia
AIMS OF THIS THESIS
MATERIALS AND METHODS
Subjects, animals
Dissection of VM, frontal cortex, LGE, and raphe dorsalis
Organotypic primary cultures
Intracranial (ventricular) grafting (GDNF)
Enzyme-linked immunosorbent assay
Genotyping
Dopamine lesions
Behavioral testing
In vivo chronoamperometry
Intraocular transplantation
Tissue preparation and brain sectioning
Immunohistochemistry
Image analysis
Statistics
RESULTS AND DISCUSSION
Characterization of rat fetal VM slice cultures, paper I
Different nerve fiber growth patterns depending on culture technique
Glial cells in rat fetal VM cultures
Effects of GDNF on mice fetal VM slice cultures, paper II
GDNF protein levels in culture medium and fetal brain
TH-positive neuronal survival in the absence of GDNF
The effect of GDNF on astrocytes
The importance of GDNF for midbrain dopaminergic neurons and nerve fiber formation
Inhibition of astroglia in rat fetal VM cultures, paper III
Importance of fetal age upon grafting
Radial glia in VM cultures
Fetal VM and cortex co-cultures
Dopaminergic subpopulations in fetal VM cultures
Grafting of fetal midbrain dopamine neurons
Effects of L-DOPA in a rat model of dyskinesia, paper IV
AIMs ratings
In vivo chronoamperometry, electrochemical recordings
TH-positive nerve fiber density
SERT-positive nerve fiber density
The conversion of L-DOPA to dopamine in dopamine-depleted striatum, paper V
Different L-DOPA phenomena
Effects of local striatal ejections of L-DOPA
Evaluation of the SERT-positive nerve fiber density…
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Author: af Bjerkén, Sara
Source: Umea University