Protection by the NDI1 gene against neurodegeneration in a rotenone rat model of Parkinson's disease

Marella, M and Seo, BB and Nakamaru-Ogiso, E and Greenamyre, JT and Matsuno-Yagi, A and Yagi, T (2008) Protection by the NDI1 gene against neurodegeneration in a rotenone rat model of Parkinson's disease. PLoS ONE, 3 (1).

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Abstract

It is widely recognized that mitochondrial dysfunction, most notably defects in the NADH-quinone oxidoreductase (complex I), is closely related to the etiology of sporadic Parkinson's disease (PD). In fact, rotenone, a complex I inhibitor, has been used for establishing Pl) models both in vitro and in vivo. A rat model with chronic rotenone exposure seems to reproduce pathophysiological conditions of PD more closely than acute mouse models as manifested by neuronal cell death in the substantia nigra and Lewy body-like cytosolic aggregations. Using the rotenane rat model, we investigated the protective effects of alternative NADH dehydrogenase (Ndl1) which we previously demonstrated to act as a replacement for complex I both in vitro and in vivo. A single, unilateral injection of recombinant adena-associated virus carrying the NDl1 gene into the vicinity of the substantia nigra resulted in expression of the Ndl1 protein in the entire substantia nigra of that side. It was clear that the introduction of the Ndl1 protein in the substantia nigra rendered resistance to the deleterious effects caused by rotenone exposure as assessed by the levels of tyrosine hydroxylase and dopamine. The presence of the Ndl1 protein also prevented cell death and oxidative damage to DNA in dopaminergic neurons observed in rotenone-treated rats. Unilateral protection also led to uni-directional rotation of the rotenone-exposed rats in the behavioral test. The present study shows, for the first time, the powerful neuroprotective effect offered by the Ndl1 enzyme in a rotenone rat model of PD. © 2008 Marella et al.

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Details

Item Type:	Article
Status:	Published
Creators/Authors:	Creators Email Pitt Username ORCID Marella, M Seo, BB Nakamaru-Ogiso, E Greenamyre, JT Tim.Greenamyre@pitt.edu JGREENA Matsuno-Yagi, A Yagi, T
Contributors:	Contribution Contributors Name Email Pitt Username ORCID Editor Waldvogel, Henry UNSPECIFIED UNSPECIFIED UNSPECIFIED
Date:	16 January 2008
Date Type:	Publication
Journal or Publication Title:	PLoS ONE
Volume:	3
Number:	1
DOI or Unique Handle:	10.1371/journal.pone.0001433
Refereed:	Yes
PubMed ID:	18197244
Date Deposited:	18 Jul 2012 21:02
Last Modified:	04 Feb 2019 15:58
URI:	http://d-scholarship.pitt.edu/id/eprint/12929

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