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Mitochondrial involvement in neurode...

Pickrell, Alicia M.

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Mitochondrial involvement in neurodegeneration and aging.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Mitochondrial involvement in neurodegeneration and aging./
Author:	Pickrell, Alicia M.
Description:	213 p.
Notes:	Source: Dissertation Abstracts International, Volume: 74-02(E), Section: B.
Contained By:	Dissertation Abstracts International74-02B(E).
Subject:	Biology, Neuroscience. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3539119
ISBN:	9781267628602

Mitochondrial involvement in neurodegeneration and aging.
Pickrell, Alicia M.

Mitochondrial involvement in neurodegeneration and aging. - 213 p.

Source: Dissertation Abstracts International, Volume: 74-02(E), Section: B.

Thesis (Ph.D.)--University of Miami, 2012.

Mitochondrial DNA (mtDNA) damage and oxidative phosphorylation deficiency have been associated with neurodegenerative disease and aging. I hypothesized that different neuronal populations handle the respiratory chain dysfunctions differently and that different cell types also mediate different responses to mtDNA damage.

ISBN: 9781267628602Subjects--Topical Terms:

1017680
Biology, Neuroscience.

Mitochondrial involvement in neurodegeneration and aging.
LDR:02805nam a2200313 4500 001 1968976
005 20141219110806.5
008 150210s2012 ||||||||||||||||| ||eng d
020 $a 9781267628602
035 $a (MiAaPQ)AAI3539119
035 $a AAI3539119
040 $a MiAaPQ $c MiAaPQ
100 1 $a Pickrell, Alicia M. $3 2106219
245 1 0 $a Mitochondrial involvement in neurodegeneration and aging.
300 $a 213 p.
500 $a Source: Dissertation Abstracts International, Volume: 74-02(E), Section: B.
500 $a Adviser: Carlos T. Moraes.
502 $a Thesis (Ph.D.)--University of Miami, 2012.
520 $a Mitochondrial DNA (mtDNA) damage and oxidative phosphorylation deficiency have been associated with neurodegenerative disease and aging. I hypothesized that different neuronal populations handle the respiratory chain dysfunctions differently and that different cell types also mediate different responses to mtDNA damage.
520 $a We used a transgenic mouse model under the tetracycline response system to temporally and spatially control the expression of a mitochondrial-targeted restriction endonuclease, mito-PstI. Using different neuronal drivers to induce the expression of mito-PstI, we were able to elicit mtDNA double strand break damage causing an OXPHOS deficiency in vivo (Chapter 2 and 3). We then were able to follow the progressive neurodegenerative events as a result of the mitochondrial dysfunction to discover that certain neuroanatomical regions were more susceptible to OXPHOS deficiency (Chapter 2). We also observed that mitochondrial dysfunction selectively impairs axonal processes before cell bodies leading to behavioral deficits prior to complete neuronal demise (Chapter 3). Finally, we developed a ubiquitous systemic model under the Rosa26 promoter to examine how different cell types handle transient mtDNA damage (Chapter 4). Our animals had a progressive premature aging phenotype; however, we could not attribute our phenotypes to the mtDNA deletions commonly thought to participate in the aging process. We discovered a novel p53 transcriptional response after mtDNA damage that may directly or partially account for the cellular senescence present in these mice later in life.
520 $a In conclusion, we demonstrate that mitochondrial decline and mtDNA damage impacts different cell types in different ways. Future studies need to concentrate on how other neuronal and glial cell types are impacted by mitochondrial decline, and how p53 signals from the mitochondria to the nucleus.
590 $a School code: 0125.
650 4 $a Biology, Neuroscience. $3 1017680
650 4 $a Biology, Molecular. $3 1017719
650 4 $a Health Sciences, Aging. $3 1669845
690 $a 0317
690 $a 0307
690 $a 0493
710 2 $a University of Miami. $b Neuroscience (Medicine). $3 2106220
773 0 $t Dissertation Abstracts International $g 74-02B(E).
790 $a 0125
791 $a Ph.D.
792 $a 2012
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3539119