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dc.contributor.authorTian, Feng
dc.date.accessioned2018-12-20T08:11:04Z
dc.date.created2017-03
dc.date.issued2017-01-06
dc.date.submitted2017
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:37944971*
dc.description.abstractAmyotrophic lateral sclerosis (ALS) is a fast progressing motor neuron disease. Generally, the survival time of an ALS patient after diagnosis is from 3 to 5 years. The early detection of ALS related pathological features in either rodent models or patients would greatly promote the drug development and the treatment of this relentless disease. This thesis mainly concentrates on the imaging of pre-symptomatic nerve degeneration based on the label-free Stimulated Raman Scattering (SRS) microscopic imaging tools. We have found that the deposition of peripheral myelin debris (termed lipid ovoids) coincides with the earliest detectable alteration in SOD1G93A mouse model of ALS by both ex vivo and in vivo SRS imaging. Similar lipid ovoid deposition patterns have also been visualized and quantified in SOD1G37R, FUS, C9ORF72 repeat expansion and TDP43 mouse models of ALS. This study has also verified that serial SRS imaging on live mouse models enables pre-symptomatic evaluation of ALS therapeutic, which can tremendously shorten the period of time for drug screening. More importantly, lipid ovoid deposition has also been visualized by SRS imaging in the ventral roots (motor nerve fibers) but not the dorsal roots (sensory nerve fibers) of ALS patient autopsies. SRS imaging of other neurodegenerative mouse models including nerve crush and demyelination has implicated that the occurrence of lipid ovoids may be a result of initial motor axon degeneration. Thus, SRS imaging can be used as a sensitive means of quantitatively visualizing disease progression and therapeutic intervention of ALS mouse models, which would potentially galvanize future studies on disease mechanism and drug development of this disease.
dc.description.sponsorshipBiology, Molecular and Cellular
dc.format.mimetypeapplication/pdf
dc.language.isoen
dash.licenseLAA
dc.subjectBiology, Neuroscience
dc.titlePeripheral Myelin Degeneration in Amyotrophic Lateral Sclerosis Revealed by Stimulated Raman Scattering Imaging
dc.typeThesis or Dissertation
dash.depositing.authorTian, Feng
dc.date.available2018-12-20T08:11:04Z
thesis.degree.date2017
thesis.degree.grantorGraduate School of Arts & Sciences
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy
dc.contributor.committeeMemberCohen, Adam
dc.contributor.committeeMemberEngert, Florian
dc.contributor.committeeMemberArlotta, Paola
dc.type.materialtext
thesis.degree.departmentBiology, Molecular and Cellular
dash.identifier.vireohttp://etds.lib.harvard.edu/gsas/admin/view/1325
dc.description.keywordsAmyotrophic lateral sclerosis; stimulated Raman scattering
dash.author.emailftianmcb@gmail.com


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