dc.contributor.author |
Dia, Batoul Ali |
dc.date.accessioned |
2022-09-29T13:26:20Z |
dc.date.available |
2022-09-29T13:26:20Z |
dc.date.issued |
2017 |
dc.date.submitted |
2017 |
dc.identifier.other |
b20615814 |
dc.identifier.uri |
http://hdl.handle.net/10938/23636 |
dc.description |
Thesis M.Sc American University of Beirut. Department of Anatomy, Cell Biology and Physiological Siences 2017. W 4 D536m 2017; Advisor: Dr. Assaad Antoine Eid, Associate Professor, Department of Anatomy, Cell Biology and Physiological Sciences ; Committee members: Dr. Samir Atweh, Professor and Chairperson, Department of Neurology ; Dr. Nada Lawand, Assistant Professor, Department of Neurology ; Dr. Ali Eid, Assistant Professor, Department of Pharmacology and Toxicology, Dr. Youssef Zeidan, Assistant Professor, Department of Radiation Oncology. |
dc.description |
Includes bibliographical references (leaves 50-66) |
dc.description.abstract |
Background: Diabetic Neuropathy (DN) is one of the microvascular complications associated with diabetes. The clinical manifestations of DN include sensorimotor loss, paresthesia and altered pain and thermal perception. Hyperglycemia has been reported to be one of the triggers that induce peripheral nerve injury, characterized by myelin abnormalities, axonal atrophy and blunted regenerative potential. Nevertheless, the pathways that lead to the pathophysiology of diabetes-induced peripheral nerve injury has yet to be elucidated. Our group has identified reactive oxygen species (ROS) as a final key mediator in a number of diabetic complications, but their role in the etiology of DN has not been previously described. One of the major sources of ROS is the NADPH Oxidases (NOX) family, which we and others have shown to be involved in the pathophysiology of diabetic complications. More importantly, the crosstalk of NADPH oxidases with downstream or upstream signaling molecules is at the heart of the deleterious effect seen in diabetic complications. Aim: The following study aims to investigate the role of NOX1 enzyme as sources of oxidative stress in myelinating Schwann cells (SCs) and sciatic nerves in the diabetic milieu. Furthermore, the crosstalk of the NADPH oxidases with the mTOR signaling pathway and the role of this signaling axe in SCs and sciatic nerve injury will be identified. Methods: Mouse Schwann Cell (MSC80) cell line are used for in vitro studies and the C57-BL6, NOD-FVB, and Swiss Webster mice are used for the in vivo studies. Western blot and PCR analyses are used to assess expression of myelin proteins, NOXs, mTOR complexes associated proteins in addition to their signaling effectors. In vitro silencing of NOX and mTOR is also performed by transfection to further elucidate the role of the NOX-mTOR axe in diabetic peripheral injury. NADPH oxidase activity assay is used to assess NADPH-induced intracellular ROS production alongside DHE staining, and HPLC in SCs and sciatic nerves. Cellular apoptoti |
dc.format.extent |
1 online resource (66 leaves) |
dc.language.iso |
eng |
dc.subject.classification |
D536m 2017 |
dc.subject.lcsh |
Dissertations, Academic.||Schwann Cells.||Diabetes. |
dc.title |
mTOR complexes promote peripheral nerve damage and Schwann cell injury in diabetes |
dc.type |
Thesis |
dc.contributor.department |
Department of Anatomy, Cell Biology and Physiological Sciences |
dc.contributor.institution |
American University of Beirut |
dc.contributor.authorFaculty |
Faculty of Medicine |