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Title: The effects of oxidative stress on synapse development in Drosophila
Author: Milton, Valerie
ISNI:       0000 0004 2721 5773
Awarding Body: University of York
Current Institution: University of York
Date of Award: 2011
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Mutations in spinster, a late-endosomal/ lysosomal protein have been shown to cause overgrowth of the Drosophila neuromuscular junction, coupled with impaired synaptic transmission (Sweeney and Davies, 2002). Oxidative stress is implicated in many neurodegenerative disorders; however, its effects on development are still unclear. In this thesis, it is shown that oxidative stress is implicated in the development of the spinster phenotype; overgrowth of the NMJ is rescued by over-expression of superoxide-dismutase (SOD) and catalase, components of the anti-oxidant defence system. Overgrowth can also be caused by oxidative stress in the absence of lysosomal dysfunction; synapse overgrowth is also observed in mutants defective for protection from ROS, and animals subjected to excessive ROS. The data shown here also indicate that spinster and oxidative stress induced overgrowth requires ASK/JNK/AP-1 signalling pathways, attenuating ASK/JNK/AP-1 activity reduces overgrowth. Genes required for autophagy (Atg1 and Atg18) are also required for overgrowth, thus it is suggested that autophagy and JNK signalling are linked in NMJ development and dysregulated JNK/AP-1 signalling is involved in the generation of the neuronal phenotype observed in spinster. spinster and oxidative stress mutants also have impaired physiology showing reduced crawling speed and impaired synaptic transmission. AMPK is also required for spinster overgrowth, suggesting an energy deficit, supported by the presence of aberrant mitochondria.
Supervisor: Sweeney, Sean Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available