Dissociation of progressive dopaminergic neuronal death and behavioral impairments by bax deletion in a mouse model of parkinson's diseases

Tae Woo Kim, Younghye Moon, Kyungjin Kim, Jeong Eun Lee, Hyun Chul Koh, Im Joo Rhyu, Hyun Kim, Woong Sun

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Article numbere25346
JournalPLoS One
Volume6
Issue number10
DOIs
Publication statusPublished - 2011 Oct 17

Fingerprint

Parkinson disease
Dopaminergic Neurons
Oxidopamine
Neurons
Parkinson Disease
neurons
animal models
Apoptosis Inducing Factor
death
apoptosis
atrophy
Atrophy
mice
Chemical activation
movement disorders
Corpus Striatum
therapeutics
neurotoxins
Gene Deletion
Neurotoxins

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Dissociation of progressive dopaminergic neuronal death and behavioral impairments by bax deletion in a mouse model of parkinson's diseases. / Kim, Tae Woo; Moon, Younghye; Kim, Kyungjin; Lee, Jeong Eun; Koh, Hyun Chul; Rhyu, Im Joo; Kim, Hyun; Sun, Woong.

In: PLoS One, Vol. 6, No. 10, e25346, 17.10.2011.

Research output: Contribution to journalArticle

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