Journal
MOVEMENT DISORDERS
Volume 22, Issue 3, Pages 403-407Publisher
WILEY-LISS
DOI: 10.1002/mds.21306
Keywords
Parkinson's disease; proteasome; PSI; mouse model; ethanol; neurotoxicity
Categories
Funding
- NINDS NIH HHS [R21 NS43773] Funding Source: Medline
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Defects in the ubiquitin-proteasome system have been implicated in Parkinson's Disease (PD). Recently, a rat model of PD was developed using a synthetic proteasome inhibitor (PSI), (Z-Ile-Glu(OtBu)-Ala-Leu-al). We attempted to transfer this model to mouse studies, where genetics can be more readily investigated due to the availability of genetically modified mice. We treated C57BL/6 (B6) mice with six intraperitoneal injections of 6 mg/kg PSI in 50 mu l of 70% ethanol over a 2-week-period. We found significant decreases in nigrostriatal dopamine in PSI-treated mice compared with saline-treated mice. However, we observed similar decreases in the ethanol-treated vehicle control group. Administration of ethanol alone led to significant long-term alterations in dopamine levels. Ethanol significantly eclipses the effects of PSI in the dopamine system, and therefore is a confounding vehicle for this model. (C) 2007 Movement Disorder Society.
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