Article ID Journal Published Year Pages File Type
328706 Neurobiology of Aging 2009 10 Pages PDF
Abstract

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.

Related Topics
Life Sciences Biochemistry, Genetics and Molecular Biology Ageing
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