1-methyl-4-phenylpyridinium neurotoxicity is attenuated by adenoviral gene transfer of human Cu/Zn superoxide dismutase
✍ Scribed by Martine Barkats; Philippe Horellou; Philippe Colin; Stéphanie Millecamps; Nicole Faucon-Biguet; Jacques Mallet
- Publisher
- John Wiley and Sons
- Year
- 2006
- Tongue
- English
- Weight
- 480 KB
- Volume
- 83
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
Abstract
Oxidative stress has been suggested to be an important mediator of dopaminergic cell death in Parkinson's disease (PD). We investigated the neuroprotective potential of Cu/Zn superoxide dismutase (SOD1) overexpression in the rat substantia nigra (SN) following adenovirus‐mediated gene transfer. Human dopaminergic SK‐N‐SH cells were transduced with adenoviral vectors expressing either human SOD1 (Ad‐SOD1) or β‐galactosidase (Ad‐βgal) before exposure to 1 mM of the 1‐methyl‐4‐phenylpyridinium ion (MPP^+^). A strong neuroprotective effect of SOD1 gene transfer was observed in the SK‐N‐SH cells exposed to MPP^+^ compared with controls. Adult rats were then given unilateral injections of either Ad‐SOD1 or Ad‐βgal into the striatum, and MPP^+^ was administered 8 days later at the same location. Strong transgene expression was detected in the SN dopaminergic neurons, a consequence of retrograde axonal transport of the adenoviral particles. The amphetamine‐induced rotational behavior of the rats was markedly lower in Ad‐SOD1‐injected rats than in control animals. Also, behavioral recovery significantly correlated with the number of tyrosine hydrolase‐expressing neurons in the SN of the treated rats. These results are consistent with oxidative stress contributing to the MPP^+^‐induced neurodegenerative process. They also indicate that SOD1 gene transfer into the nigrostriatal system may be a potential neuroprotective strategy for treating PD. © 2005 Wiley‐Liss, Inc.