Abstract
The role of insulin-like growth factor 1 (IGF1) pathway as regulator of aging and age-related diseases is increasingly recognized. Recent evidence has been provided that neuronal IGF1-R increases during aging leading to activation of a signaling pathway that causes an increased production of amyloid β-peptide, the principal event in the pathogenesis of Alzheimer’s disease. Here, by using long-term neuronal cultures as a model of aging, we show that astroglial cells are required to upregulate the expression of IGF1-R in neurons during in vitro senescence. Moreover, evidence is provided that the cross-talk between astrocytes and neurons is independent of cell-to-cell contact, and it is mediated by low molecular weight soluble factor(s) released by astrocytes in culture medium. These results suggest that astrocytes could play an important role in aging and age-related pathological processes.
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Abbreviations
- Aβ:
-
Amyloid β-peptides
- ACM:
-
Astrocyte-conditioned medium
- AD:
-
Alzheimer’s disease
- Ara-C:
-
Cytosine arabinoside
- CM:
-
Conditioned medium
- GFAP:
-
Glial fibrillary acid protein
- IGF1:
-
Insulin-like growth factor 1
- IGF1-R:
-
Insulin-like growth factor 1 receptor
- MAP2:
-
Microtubule-associated protein 2
- unCM:
-
Unconditioned medium
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Acknowledgments
This work was supported by University of Verona and Fondazione Cariverona. The authors are grateful to Jan Johansson for his help with the cell cultures.
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Supplementary Fig. 1
IGF1-R in primary astrocyte cultures. A Western blot analysis of IGF1-R expression in primary astrocytes after 5 (lane 3) and 15 days (lane 4) of culture in Neurobasal medium supplemented with B27 in comparison with IGF1-R expression in Ara-C-treated (lane 1) and neuron-enriched cortical cultures (lane 2) at day 15. Data are representative of two experiments. B, C Confocal images of primary astrocytes double stained with anti-GFAP (green) and anti-IGF1-R (red) antibodies. Nuclei are stained with DAPI (blue). Astrocytes were maintained in culture in Neurobasal medium plus B27 for 5 days before staining. Scale bars = 25 μm. Images are from one experiment representative of three (GIFF 137 kb)
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Costantini, C., Lorenzetto, E., Cellini, B. et al. Astrocytes Regulate the Expression of Insulin-Like Growth Factor 1 Receptor (IGF1-R) in Primary Cortical Neurons During In Vitro Senescence. J Mol Neurosci 40, 342–352 (2010). https://doi.org/10.1007/s12031-009-9305-5
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DOI: https://doi.org/10.1007/s12031-009-9305-5