Altered expression of IGF‐I system in neurons of the inflamed spinal cord during acute experimental autoimmune encephalomyelitis

Abstract

There is growing evidence that the impaired IGF-I system contributes to neurodegeneration. In this study, we examined the spinal cords of the EAE, the animal model of multiple sclerosis, to see if the expression of the IGF-I system is altered. To induce EAE, C57/BL6 mice were immunized with the Hooke lab MOG kit, sacrificed at the peak of the disease and their spinal cords were examined for the immunoreactivities (ir) of the IGF-I, IGF binding protein-1 (IGFBP-1) and glycogen synthase kinase 3β (GSK3β), as one major downstream molecule in the IGF-I signaling. Although neurons in the non EAE spinal cords did not show the IGF-I immunoreactivity, they were numerously positive for the IGFBP-1. In the inflamed EAE spinal cord however, the patterns of expressions were reversed, that is, a significant increased number of IGF-I expressing neurons versus a reduced number of IGFBP-1 positive neurons. Moreover, while nearly all IGF-I-ir neurons expressed GSK3β, some expressed it more intensely. Considering our previous finding where we showed a significant reduced number of the inactive (phosphorylated) but not that of the total GSK3β expressing neurons in the EAE spinal cord, it is conceivable that the intense total GSK3β expression in the IGF-I-ir neurons belongs to the active form of GSK3β known to exert neuroinflammatory effects. We therefore suggest that the altered expression of the IGF-I system including GSK3β in spinal cord neurons might involve in pathophysiological events during the EAE.

Proteomic Analysis of Huntington’s Disease Medium Spiny Neurons Identifies Alterations in Lipid Droplets

“…IGFBP7 is released by senescent cells, and cellular senescence is a pathway we previously identified as activated in HD-MSNs with a multitude of relevant markers, including IGFBP7 mRNA ( 60 ). IGFBPs are biomarkers for multiple diseases, and their expression causes neurodegeneration ( 61 , 62 , 63 , 64 , 65 , 66 , 67 ). Western blot analysis further validated the increased levels of IGFBP7 in HD72-MSNs ( supplemental Fig.…”

Neurite Growth and Polarization on Vitronectin Substrate after in Vitro Trauma is not Enhanced after IGF Treatment

“…Our findings of vitronectin as favorable compared to the control (Figure 2 and Figure 4) was thus not unexpected. Recent studies have also shown that intraventricular administration of IGF-1 after experimental traumatic brain injury results in the enhanced generation of immature hippocampal neurons in the granular layer of the dentate gyrus [11] and that an impaired IGF-1 system contributes to neurodegeneration in inflammatory disorders in CNS [34]. These findings could support the notion that IGF-1 is of importance in CNS injuries, even though the picture is far from fully understood regarding the fine tuning of the IGF/IGFBP/vitronectin complex in the nervous system.…”