| First Author | Nadjar A | Year | 2009 |
| Journal | Neurobiol Aging | Volume | 30 |
| Issue | 12 | Pages | 2021-30 |
| PubMed ID | 18394756 | Mgi Jnum | J:155157 |
| Mgi Id | MGI:4412359 | Doi | 10.1016/j.neurobiolaging.2008.02.009 |
| Citation | Nadjar A, et al. (2009) IGF-1 signaling reduces neuro-inflammatory response and sensitivity of neurons to MPTP. Neurobiol Aging 30(12):2021-30 |
| abstractText | 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. |
