کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
328706 1433627 2009 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
IGF-1 signaling reduces neuro-inflammatory response and sensitivity of neurons to MPTP
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
IGF-1 signaling reduces neuro-inflammatory response and sensitivity of neurons to MPTP
چکیده انگلیسی

Reduced expression of IGF-1R increases lifespan and resistance to oxidative stress in the mouse, raising the possibility that this also confers relative protection against the pro-parkinsonian neurotoxin MPTP, known to involve an oxidative stress component. We used heterozygous IGF-1R+/− mice and challenged them with MPTP. Interestingly, MPTP induced more severe lesions of dopaminergic neurons of the substantia nigra, in IGF-1R+/− mice than in wild-type animals. Using electron spin resonance, we found that free radicals were decreased in IGF-1R+/− mice in comparison with controls, both before and after MPTP exposure, suggesting that the increased vulnerability of dopamine neurons is not caused by oxidative stress. Importantly, we showed that IGF-1R+/− mice display a dramatically increased neuro-inflammatory response to MPTP that may ground the observed increase in neuronal death. Microarray analysis revealed that oxidative stress-associated genes, but also several anti-inflammatory signaling pathways were downregulated under control conditions in IGF-1R+/− mice compared to WT. Collectively, these data indicate that IGF signaling can reduce neuro-inflammation dependent sensitivity of neurons to MPTP.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Aging - Volume 30, Issue 12, December 2009, Pages 2021–2030
نویسندگان
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