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STUDIES ON PLASTICITY AND NEURODEGENERATION IN RAT
HIPPOCAMPUS
by
Miou Zhou
A Dissertation presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(NEUROSCIENCE)
December 2008
Copyright 2008 Miou Zhou
Object Description
| Title | Studies on plasticity and neurodegeneration in rat hippocampus |
| Author | Zhou, Miou |
| Author email | miouzhou@usc.edu; zhoumiou@hotmail.com |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Neuroscience |
| School | College of Letters, Arts and Sciences |
| Date defended/completed | 2008-08-07 |
| Date submitted | 2008 |
| Restricted until | Unrestricted |
| Date published | 2008-09-16 |
| Advisor (committee chair) | Baudry, Michel |
| Advisor (committee member) |
Thompson, Richard Ko, Chien-Ping Qin, Peter |
| Abstract | Oxygen/glucose deprivation (OGD) is widely used as an in vitro model of ischemia, and mechanisms underlying OGD-induced neuronal death are not completely understood. I tested the participation of reactive oxygen species (ROS) in OGD by using EUK-207, a synthetic superoxide dismutase/catalase mimetic. EUK-207 provides neuroprotection against OGD-induced cell death both in acute and cultured hippocampal slices. In cultured slices, this effect is related to decreased free radical accumulation, reduced release of apoptosis-inducing factor and reduced lipid peroxidation. In acute slices, protective effects of EUK-207 are also related to elimination of free radical accumulation and partial reversal of ATP depletion. Excitotoxicity induced by overactivation of NMDA receptors, a subtype of ionotropic glutamate receptors, is involved in OGD-induced cell death in slices from young but not adult rats. To better understand the mechanisms of excitotoxic cell death, I studied the effects of NMDA treatment on acute hippocampal slices from both neonatal and mature rats, and in particular, the role of calpain-mediated spectrin degradation. NMDA treatment results in cell death and spectrin degradation in slices from young but not adult rats, effects that are partly abolished by NMDA receptor subunit NR2B antagonists and by calpain inhibitor III, but not affected by a NR2A specific antagonist, suggesting that developmental changes in NMDA receptor subunit composition contribute to developmental changes in NMDA toxicity and possibly OGD-induced cell death.; While overactivation of NMDA receptors is involved in neurodegeneration, modulation of AMPA receptors, another ionotropic glutamate receptor subtype, is involved in synaptic plasticity. Positive AMPA receptor modulators (such as CX614) facilitate LTP induction and improve performance in several learning tasks. We demonstrated that CX614 rapidly activates the dendritic translation machinery and increases the dendritic expression of Arc, a translation reporter, in a brain-derived neurotrophic factor- (BDNF) dependent manner. AMPA receptor activation, extracellular calcium influx, intracellular calcium release, and activation of BDNF receptor TrkB, are all required for CX614-induced effects on protein translation, indicating that BDNF secretion is involved in these effects. Our results demonstrate that positive modulation of AMPA receptors stimulates AMPA receptor- and TrkB receptor- dependent dendritic protein translation, an effect mediated by BDNF secretion. |
| Keyword | plasticity; neurodegeneration; hippocampus; ischemia; excitotoxicity; ampakine |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m1600 |
| Rights | Zhou, Miou |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | http://www.usc.edu/isd/libraries/services/ask_a_librarian/email/ |
| Filename | etd-Zhou-2374 |
| Archival file | uscthesesreloadpub_Volume23/etd-Zhou-2374.pdf |
Description
| Title | Page 1 |
| Full text | STUDIES ON PLASTICITY AND NEURODEGENERATION IN RAT HIPPOCAMPUS by Miou Zhou A Dissertation presented to the FACULTY OF THE GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (NEUROSCIENCE) December 2008 Copyright 2008 Miou Zhou |
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