Blunting Type 1 Insulin-like Growth Factor Receptor Expression Exacerbates Neuronal Apoptosis Following Hypoxic/Ischemic Injury Public Deposited

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  • D'Ercole, Joseph A.
    • Affiliation: School of Medicine, Department of Pediatrics
  • Liu, Wen
    • Affiliation: School of Medicine, Department of Pediatrics
  • Ye, Ping
    • Affiliation: School of Medicine, Department of Pediatrics
  • Abstract Background Abundant experimental data have implicated an important role for insulin-like growth factor (IGF) in protecting neuronal cells from injury, including hypoxia/ischemia (H/I) injury, a major cause of neuron death. While the specific interaction of IGFs with neuronal or glial type 1 IGF receptors (IGF1R) has been shown to be essential to IGF actions during development, the same has not been directly demonstrated following H/I injury. To directly examine the role of neuronal IGF1R following H/I injury, we utilized conditional mutant nes-igf1r -/Wt mice and determined the impact of IGF1R haplodeficiency specifically in nestin-expressing neuronal precursors and their progeny on H/I-induced neuronal damage and apoptosis in hippocampus. Results H/I induced significant damage to the cerebral hemisphere and hippocampus ipsilateral to the ligated right common carotid artery both in control and nes-igf1r -/Wt mice at postnatal day 10. Blunting IGF1R expression, however, markedly exacerbated H/I-induced damage and appeared to increase mortality. In the ipsilateral hemisphere and hippocampus, nes-igf1r -/Wt mice had infarct areas double the size of those in controls. The size of the ipsilateral hemisphere and hippocampus in nes-igf1r -/Wt mice were 15% to 17% larger than those in controls, reflecting more severe edema. Consistent with its effects on infarct area, IGF1R haplodeficiency causes a greater decrease in neurons in the ipsilateral hippocampus of nes-igf1r -/Wt mice. The reduction in neurons was largely due to increases in neuronal apoptosis. Judged by pyknotic nuclei, TUNEL and caspase-3 labeling, nes-igf1r -/Wt mice had significantly more apoptotic cells than that in controls after injury. To determine possible mechanisms of IGF1R actions, the mRNA expression of the pro-survival proteins IAP-1 and XIAP was determined. Compared to controls, the abundance of cIAP-1 and XIAP mRNA was markedly suppressed in mice with blunted IGF1R or IGF-I expression, while was increased in the brain of IGF-I overexpressing transgenic mice. Conclusion IGF1R in neuronal cells is critically important for their survival following H/I injury, and IGF-upregulated expression of neuronal cIAP-1 and XIAP likely in part contributes to IGF-IGF1R protection against neuronal apoptosis following H/I injury.
Date of publication
  • doi:10.1186/1471-2202-12-64
  • 21718528
Resource type
  • Article
Rights statement
  • In Copyright
Rights holder
  • Wen Liu et al.; licensee BioMed Central Ltd.
Journal title
  • BMC Neuroscience
Journal volume
  • 12
Journal issue
  • 1
Page start
  • 64
  • English
Is the article or chapter peer-reviewed?
  • Yes
  • 1471-2202
Bibliographic citation
  • BMC Neuroscience. 2011 Jun 30;12(1):64
  • Open Access
  • BioMed Central Ltd

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