کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2590532 1131751 2006 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
In vivo modulation of the Parkinsonian phenotype by Nrf2
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
In vivo modulation of the Parkinsonian phenotype by Nrf2
چکیده انگلیسی

Oxidative stress has been implicated in the etiology of Parkinson's disease (PD) and in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal model of PD. In this report we show that Nrf2, a transcription factor that regulates the expression of phase 2 and antioxidative enzymes, modulates MPTP neurotoxicity in rodents. Nrf2 knockout and wild-type mice were administered MPTP doses ranging from 20 to 60 mg/kg. Seven days after MPTP administration dopamine transporter (DAT) levels were measured using [125I]-RTI-121 quantitative autoradiography as an index of dopamine terminal integrity in the striatum. The results indicate that MPTP administration resulted in a greater loss of DAT levels in the striatum of Nrf2 knockout mice than in wild-type at all MPTP doses tested. Activation of the Nrf2 pathway by oral administration of the Nrf2 inducer 3H-1,2-dithiole-3-thione (D3T) to wild-type mice produced partial protection against MPTP-induced neurotoxicity. The protective effect of D3T was not due to a change in MPTP metabolism since the level of the MPTP metabolite MPP+ was not significantly different in the D3T treated striatum relative to vehicle control. Administration of D3T to Nrf2 knockout mice did not protect against MPTP neurotoxicity suggesting that the Nrf2 pathway is necessary for the D3T-mediated attenuation of MPTP neurotoxicity. This study demonstrates the significance of activating intrinsic antioxidative mechanisms in an in vivo model of neurodegeneration. The in vivo activation of the Nrf2 pathway in the brain may be an important strategy to mitigate the effects of oxidative stress in neurodegenerative disorders and neurological disease.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: NeuroToxicology - Volume 27, Issue 6, December 2006, Pages 1094–1100
نویسندگان
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