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dc.contributor.authorMcLoed, Melissaen_US
dc.date.accessioned2016-01-12T16:06:32Z
dc.date.issued2015
dc.identifier.urihttps://hdl.handle.net/2144/13983
dc.description.abstractFollowing neuronal injury, calcium signaling plays a critical role in promoting repair processes. Injury produces an initial cytosolic calcium elevation mediated by calcium entry from the cut site, plasma membrane channels, and intracellular storage compartments. Subsequently, a variety of signaling factors are involved in promoting growth cone formation and axon outgrowth and guidance, some of which include DLK-1, CaMP, CED-3, CED-4, and calreticulin. Specific proteins mediating calcium transport have also been reported to significantly affect regenerative outgrowth, particularly inositol triphosphate receptors, voltage-gated calcium channels, and ryanodine receptors. Given that mitochondria can store intracellular calcium and regulate cytosolic calcium levels, we hypothesized that the mitochondrial uniporter (MCU) may play a significant role in neuronal regeneration. We found that inhibiting calcium entry into the mitochondria via a loss of function mutation in MCU significantly enhances axonal outgrowth following laser axotomy of single neurons in C. elegans. This effect is calcium-dependent, with the MCU mutant regenerative phenotype reverting to baseline levels when mutants are chronically treated with the calcium chelator EGTA. We also find that sub-cellular calcium signals at the axon cut site are significantly reduced in MCU mutants, while basal levels of calcium and axon guidance remain unaffected. These findings suggest that mitochondrial calcium regulation plays a significant role in the regeneration of single neurons, and that inhibition of MCU activity may be a promising avenue for the treatment of clinical syndromes derived from axonal injury, such as spinal cord injury.en_US
dc.language.isoen_US
dc.rightsAttribution 4.0 Internationalen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectNeurosciencesen_US
dc.subjectCalciumen_US
dc.subjectMitochondriaen_US
dc.titleTHE mitochondrial uniporter modulates neuronal regenerative outgrowth and calcium dynamics following axotomy in C. elegansen_US
dc.typeThesis/Dissertationen_US
dc.date.updated2015-11-03T23:08:52Z
dc.description.embargo2017-11-03T00:00:00Z
etd.degree.nameM.A.en_US
etd.degree.levelmastersen_US
etd.degree.disciplinePharmacology & Experimental Therapeuticsen_US
etd.degree.grantorBoston Universityen_US


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Attribution 4.0 International
Except where otherwise noted, this item's license is described as Attribution 4.0 International