IGF-1 signaling reduces neuro-inflammatory response and sensitivity of neurons to MPTP

Neurobiol Aging. 2009 Dec;30(12):2021-30. doi: 10.1016/j.neurobiolaging.2008.02.009. Epub 2008 Apr 3.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Death / drug effects
  • Cell Death / physiology
  • Dopamine / metabolism
  • Electron Spin Resonance Spectroscopy
  • Free Radicals / metabolism
  • MPTP Poisoning / genetics
  • MPTP Poisoning / immunology
  • MPTP Poisoning / physiopathology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neuroimmunomodulation / physiology*
  • Neurons / drug effects*
  • Neurons / immunology
  • Neurons / physiology*
  • Oligonucleotide Array Sequence Analysis
  • Oxidative Stress / drug effects
  • Oxidative Stress / genetics
  • Oxidative Stress / physiology
  • Receptor, IGF Type 1 / genetics
  • Receptor, IGF Type 1 / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Signal Transduction / physiology
  • Substantia Nigra / drug effects
  • Substantia Nigra / immunology
  • Substantia Nigra / physiology


  • Free Radicals
  • Receptor, IGF Type 1
  • Dopamine