IGF-1 signaling reduces neuro-inflammatory response and sensitivity of neurons to MPTP.
Neurobiology of Aging. 2009-12-01; 30(12): 2021-2030
DOI: 10.1016/j.neurobiolaging.2008.02.009
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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
MPTP.
Nadjar A(1), Berton O, Guo S, Leneuve P, Dovero S, Diguet E, Tison F, Zhao B,
Holzenberger M, Bezard E.
Author information:
(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.
DOI: 10.1016/j.neurobiolaging.2008.02.009
PMID: 18394756 [Indexed for MEDLINE]