Dissociation of Progressive Dopaminergic Neuronal Death and Behavioral Impairments by Bax Deletion in a Mouse Model of Parkinson's Diseases
- Authors
- Kim, Tae Woo; Moon, Younghye; Kim, Kyungjin; Lee, Jeong Eun; Koh, Hyun Chul; Rhyu, Im Joo; Kim, Hyun; Sun, Woong
- Issue Date
- 17-10월-2011
- Publisher
- PUBLIC LIBRARY SCIENCE
- Citation
- PLOS ONE, v.6, no.10
- Indexed
- SCIE
SCOPUS
- Journal Title
- PLOS ONE
- Volume
- 6
- Number
- 10
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/111363
- DOI
- 10.1371/journal.pone.0025346
- ISSN
- 1932-6203
- Abstract
- Parkinson's disease (PD) is a common, late-onset movement disorder with selective degeneration of dopaminergic (DA) neurons in the substantia nigra (SN). Although the neurotoxin 6-hydroxydopamine (6-OHDA) has been used to induce progressive degeneration of DA neurons in various animal models of PD, the precise molecular pathway and the impact of anti-apoptotic treatment on this neurodegeneration are less understood. Following a striatal injection of 6-OHDA, we observed atrophy and progressive death of DA neurons in wild-type mice. These degenerating DA neurons never exhibited signs of apoptosis (i.e., caspase-3 activation and cytoplasmic release of cytochrome C), but rather show nuclear translocation of apoptosis-inducing factor (AIF), a hallmark of regulated necrosis. However, mice with genetic deletion of the proapoptotic gene Bax (Bax-KO) exhibited a complete absence of 6-OHDA-induced DA neuron death and nuclear translocation of AIF, indicating that 6-OHDA-induced DA neuronal death is mediated by Bax-dependent AIF activation. On the other hand, DA neurons that survived in Bax-KO mice exhibited marked neuronal atrophy, without significant improvement of PD-related behavioral deficits. These findings suggest that anti-apoptotic therapy may not be sufficient for PD treatment, and the prevention of Bax-independent neuronal atrophy may be an important therapeutic target.
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Collections - Graduate School > Department of Biomedical Sciences > 1. Journal Articles
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