IGF-1 signaling reduces neuro-inflammatory response and sensitivity of neurons to MPTP.
Neurobiology of Aging. 2009-12-01; 30(12): 2021-2030
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1. Neurobiol Aging. 2009 Dec;30(12):2021-30. doi:
10.1016/j.neurobiolaging.2008.02.009. Epub 2008 Apr 3.
IGF-1 signaling reduces neuro-inflammatory response and sensitivity of neurons to
Nadjar A(1), Berton O, Guo S, Leneuve P, Dovero S, Diguet E, Tison F, Zhao B,
Holzenberger M, Bezard E.
(1)Université Victor Segalen Bordeaux 2, Centre National de la Recherche
Scientifique, Bordeaux Institute of Neuroscience, UMR 5227, Bordeaux, France.
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.
PMID: 18394756 [Indexed for MEDLINE]