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Title: The effects of macrophage-stimulating protein and gamma synuclein on the development of brainstem motor systems
Author: Schmidt, Oliver
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2002
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Here, the effects of macrophage-stimulating protein (MSP) and γ-synuclein on two systems in the developing brainstem involved in controlling movement have been studied: a) the cranial motoneurons and b) the dopaminergic neurons of the substantia nigra and the ventral tegmental area. MSP exerts a variety of biological actions on many cell types, but has no known functions in the brain. To investigate whether MSP is also capable of acting as a neurotrophic factor, hypoglossal motoneurons were purified from the embryonic chicken hindbrain because these neurons are known to express the MSP receptor tyrosine kinase RON. The study shows that MSP promotes the in vitro survival of these neurons during the period of naturally occurring neuronal cell death and enhances the growth of neurites from these neurons. Furthermore, MSP mRNA was detected in the developing tongue which is the target tissue for hypoglossal neurons. These studies demonstrate that MSP is a neurotrophic factor for a distinct population of developing motoneurons. γ-synuclein is a recently discovered member of the synuclein family. Another member of this family, α-synuclein has been implicated in the pathogenesis of Parkinson’s disease. However, little is known about the function of γ-synuclein and it has not yet been directly implicated in the genesis of neurodegenerative conditions. Here, brainstems of transgenic mice lacking γ-synuclein have been analysed by means of immunohistochemical and histological techniques. The data obtained shows that γ-synuclein is expressed in the murine substantia nigra and in most cranial motor nuclei and that the localization of the protein undergoes a shift during development from a cytosomal to an axonal and synaptic localization. Mice lacking γ-synuclein have a deficit of neurons in these structures. In the context of recent studies which have revealed in vivo and in vitro interactions between the synucleins, this data suggests that a fine balance between α- and γ-synuclein seems critical to prevent the demise of certain neurons during the period of naturally occurring cell death. It also indicates that γ-synuclein may play a role in the pathogenesis of Parkinson’s disease.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available