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Alteration of IGF system gene expression during the postnatal development of pcd mice
1Wells Center for Pediatric Research, Department of Anatomy, Division of Neuropathology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
Abstract:
IGF-I promotes growth during postnatal development via both endocrine and autocrine actions. In pcd mice (pcd/pcd), we previously found that IGF-I mRNA expression was decreased in cerebellar Purkinje cells as they underwent apoptosis. To investigate the endocrine function of IGF-I, we examined hepatic IGF-I mRNA by Northern hybridization, circulating IGF-I peptide by radioimmunoassay, and circulating IGFBP by Western ligand blot in pcd mice. At postnatal days (D) 17 and 24, hepatic IGF-I mRNA and circulating IGF-I and IGF-II concentrations were normal in pcd mice. From D45, both hepatic IGF-I mRNA and circulating IGF-I concentrations decreased. The decrease in circulating IGF-I concentrations was accompanied by a simultaneous increase in circulating IGF-II concentrations in both the D45 and adult pcd mice. An early decrease in the circulating IGFBP-3 levels and an increase in the IGFBP-2 levels were observed at D17 and were followed by decreases in both IGFBPs at D45 and in the adult. Therefore, after the cerebellar neurodegeneration, there was an overall decrease in IGF-I gene expression in pcd mice. Our results suggest that the decrease in IGF-I gene expression may contribute to growth deficiency and multiple system degeneration in pcd mice.
Insights
In pcd mice, decreased Insulin-like Growth Factor-I (IGF-I) gene expression after cerebellar degeneration may cause growth deficiency. This study investigated IGF-I
Area of Science:
- Neuroscience
- Endocrinology
- Genetics
Background:
- Insulin-like Growth Factor-I (IGF-I) is crucial for postnatal development through endocrine and autocrine pathways.
- Previous studies indicated reduced IGF-I mRNA in cerebellar Purkinje cells of pcd mice during apoptosis.
Purpose of the Study:
- To investigate the endocrine function of IGF-I in pcd mice.
- To examine hepatic IGF-I mRNA, circulating IGF-I peptide, and IGF-binding proteins (IGFBPs) in pcd mice.
Main Methods:
- Northern hybridization for hepatic IGF-I mRNA analysis.
- Radioimmunoassay for circulating IGF-I peptide quantification.
- Western ligand blot for circulating IGFBP profiling.
Main Results:
- Hepatic IGF-I mRNA and circulating IGF-I/IGF-II levels were normal at postnatal days 17 and 24 in pcd mice.
- From postnatal day 45 onwards, hepatic IGF-I mRNA and circulating IGF-I concentrations decreased, accompanied by increased IGF-II.
- Early alterations in IGFBP-3 and IGFBP-2 levels were observed, followed by decreases in both at later stages.
Conclusions:
- Cerebellar neurodegeneration in pcd mice leads to a global decrease in IGF-I gene expression.
- Reduced IGF-I gene expression is a potential contributor to the growth deficiency and multi-system degeneration observed in pcd mice.