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IGF-1 signaling reduces neuro-inflammatory response and sensitivity of neurons to MPTP.
- Source :
-
Neurobiology of aging [Neurobiol Aging] 2009 Dec; Vol. 30 (12), pp. 2021-30. Date of Electronic Publication: 2008 Apr 03. - Publication Year :
- 2009
-
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.
- Subjects :
- Animals
Cell Death drug effects
Cell Death physiology
Dopamine metabolism
Electron Spin Resonance Spectroscopy
Free Radicals metabolism
MPTP Poisoning genetics
MPTP Poisoning immunology
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Neurons immunology
Oligonucleotide Array Sequence Analysis
Oxidative Stress drug effects
Oxidative Stress genetics
Oxidative Stress physiology
Receptor, IGF Type 1 genetics
Signal Transduction drug effects
Signal Transduction genetics
Signal Transduction physiology
Substantia Nigra drug effects
Substantia Nigra immunology
Substantia Nigra physiology
MPTP Poisoning physiopathology
Neuroimmunomodulation physiology
Neurons drug effects
Neurons physiology
Receptor, IGF Type 1 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1558-1497
- Volume :
- 30
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Neurobiology of aging
- Publication Type :
- Academic Journal
- Accession number :
- 18394756
- Full Text :
- https://doi.org/10.1016/j.neurobiolaging.2008.02.009