Skip to Main Content
 

Global Search Box

 
 
 
 

Files

File List


kent1334582961.pdf (3.63 MB)

ETD Abstract Container

Abstract Header

Understanding temporal and cellular constraints involved in the development of MLV-induced spongiform neurodegeneration

Cardona, Sandra Milena
http://rave.ohiolink.edu/etdc/view?acc_num=kent1334582961

Abstract Details

2012, PHD, Kent State University, College of Arts and Sciences / School of Biomedical Sciences.
Certain murine leukemia viruses (MLVs) are capable of inducing a progressive motor neuron disease that clinically resembles amyotrophic lateral sclerosis (ALS) and results in vacuolar degeneration characteristic of prion diseases. Development of spongiosis requires neurotoxic Env protein expression within cells of the brain parenchyma, however the nature of the cell type that mediates pathology remains unresolved. Additionally, spongiosis requires developmental maturation of susceptible neural elements beyond postnatal day 10 (P10). In the first part of this study we investigated whether the P10 developmental maturation was the only requirement for neuropathology. Neural stem cell-mediated virus challenge of P10 “mature” brains revealed that neuronal susceptibility acquired at P9-10 is not sufficient to facilitate the appearance of acute spongiform changes; instead a 7-day delay in neuropathology appearance implicates the requirement for additional events beyond viral entry, spread or neurotoxic Env expression. In the second part of this document we investigated the cell type involved in the development of spongiform neurodegeneration. Here we provide evidence for a critical role of infection of astrocyte progenitors and their maturation and interaction with susceptible neurons in MLV-induced neuropathogenesis. Identification of astrocytes as novel targets of MLVs was accomplished by the utilization of transgenic mice as a readout for MLV infection, because in a scenario of sub-detectable viral protein expression, standard immunological probes in combination with cell type specific markers showed no differences in the CNS cell types infected with neurovirulent or non-neurovirulent viruses that could account for neuropathogenicity. Implication of astrocytes as critical players in MLV-induced neurodegeneration is supported by the utilization of an amphotropic virus (4070A) thought to be non-neurovirulent, but which was discovered by our laboratory to have neurotoxic effects only when pseudotyped by ecotropic Envs. This pseudotyping results in the dissemination of amphotropic neurotoxic sequences into astrocytes at a higher frequency in comparison to the restricted 4070A virus alone that infects a very low number of astrocytes and induces minimal spongiosis. Revealing the precise nature of the interactions between infected astrocytes and neuronal populations susceptible to undergoing vacuolar degeneration will provide more insight into the molecular mechanisms underlying neurodegenerative diseases.
William Lynch, PhD (Advisor)
Neurosciences

Recommended Citations

Citations

  • Cardona, S. M. (2012). Understanding temporal and cellular constraints involved in the development of MLV-induced spongiform neurodegeneration [Doctoral dissertation, Kent State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=kent1334582961

    APA Style (7th edition)

  • Cardona, Sandra. Understanding temporal and cellular constraints involved in the development of MLV-induced spongiform neurodegeneration. 2012. Kent State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=kent1334582961.

    MLA Style (8th edition)

  • Cardona, Sandra. "Understanding temporal and cellular constraints involved in the development of MLV-induced spongiform neurodegeneration." Doctoral dissertation, Kent State University, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=kent1334582961

    Chicago Manual of Style (17th edition)

kent1334582961
237
© 2012, all rights reserved.
This open access ETD is published by Kent State University and OhioLINK.