The Role of Retinoblastoma Protein in Dorsal Root Ganglion Neurons and Its Implications on Chemotherapy Induced Peripheral Neuropathy

dc.contributor.advisorLee, Hyoung-gon
dc.contributor.authorHerrera, Bianca
dc.contributor.committeeMemberMuzzio, Isabel
dc.contributor.committeeMemberMacpherson, Lindsey
dc.date.accessioned2024-02-09T22:25:11Z
dc.date.available2024-02-09T22:25:11Z
dc.date.issued2022
dc.descriptionThis item is available only to currently enrolled UTSA students, faculty or staff. To download, navigate to Log In in the top right-hand corner of this screen, then select Log in with my UTSA ID.
dc.description.abstractChemotherapy Induced Peripheral Neuropathy (CIPN) is a consequence of cancer treatments that include chemotherapeutic agents such as platinum-based compounds. While the mechanisms of CIPN are still unclear, evidence suggests that neurotoxic damage to dorsal root ganglion (DRG) sensory neurons is likely a primary mechanism. It has been shown that these therapeutic compounds induce cell cycle re-entry and cell death in DRG and is well known that cell cycle activity in neurons is highly induced in various neurodegenerative disorders. This supports a hypothesis that cell cycle re-entry mediated neurotoxicity in DRG is the underlying molecular mechanism for CIPN. To test this hypothesis, a novel transgenic mouse model (PirtRB) was established using the phosphoinositide interacting regulator of TRP (Pirt) promoter driven Cre mouse line in DRG to ablate retinoblastoma protein gene (Rb) by cross-breeding with the Rb-floxed mouse line. Rb protein, a key cell cycle regulator, prevents G1/S phase transition by binding to E2F family proteins. In PirtRB mice, the ablation of Rb in DRG induced neuronal cell loss, supporting the critical role of Rb for viability of DRG neurons. Consistently, PirtRB mice also exhibited increased mechanical allodynia, a CIPN-like neuropathic condition which supports the inactivation of Rb and subsequent cell cycle re-entry as a key molecular mechanism of the development of CIPN. Collectively, these data strongly support our hypothesis that aberrant cell cycle re-entry in DRG causes neurodegeneration and modulation of Rb-mediated cell signaling process may provide an effective therapeutic target for the treatment of CIPN.
dc.description.departmentNeuroscience, Developmental and Regenerative Biology
dc.format.extent47 pages
dc.format.mimetypeapplication/pdf
dc.identifier.isbn9798438756613
dc.identifier.urihttps://hdl.handle.net/20.500.12588/3981
dc.languageen
dc.subjectCell Cycle
dc.subjectChemotherapy
dc.subjectDRG
dc.subjectNeurodegeneration
dc.subjectPeripheral Neuropathy
dc.subjectRetinoblastoma
dc.subject.classificationNeurosciences
dc.subject.classificationBiology
dc.subject.classificationOncology
dc.subject.classificationMedicine
dc.subject.classificationBehavioral sciences
dc.titleThe Role of Retinoblastoma Protein in Dorsal Root Ganglion Neurons and Its Implications on Chemotherapy Induced Peripheral Neuropathy
dc.typeThesis
dc.type.dcmiText
dcterms.accessRightspq_closed
thesis.degree.departmentNeuroscience, Developmental and Regenerative Biology
thesis.degree.grantorUniversity of Texas at San Antonio
thesis.degree.levelMasters
thesis.degree.nameMaster of Science

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