Changes in the expression of insulin-like growth factor 1 variants in the postnatal brain development and in neonatal hypoxia-ischaemia

Int J Dev Neurosci. 2010 Feb;28(1):91-7. doi: 10.1016/j.ijdevneu.2009.09.002. Epub 2009 Sep 18.

Abstract

Insulin-like growth factor-1 (IGF-1) is a multifunctional peptide of which numerous isoforms exist. The predominant form, IGF-1Ea is involved in physiological processes while IGF-1Ec (mechano-growth factor, MGF) is expressed in response to a different set of stimuli. We have identified specific changes in the expression patterns of these IGF-1 variants in brain development in normal rats and following neonatal hypoxia-ischaemia (HI). Both IGF-1Ea and IGF-1Ec are expressed during normal postnatal brain development, albeit with highly specific temporal distributions. In contrast, HI produced increased and prolonged expression of the IGF-1Ec isoform only. Importantly, hypoxia alone stimulated the expression of IGF-1Ec as well. Thus, IGF-1Ec may play a role in HI pathology. Neonatal hypoxia-ischaemia occurs in approximately 1:4000-1:10,000 newborns and causes neurological deficits in approximately 75% of those affected. Unfortunately, no specific treatment is available. IGF-1 is known to have neuroprotective activity and its IGF-1Ec variant appears to be an endogenous protective factor in hypoxia-ischaemia. Therefore, IGF-1Ec could potentially be developed into a therapeutic modality for the attenuation or prevention of neuronal damage in this and related disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Brain / growth & development*
  • Brain / metabolism*
  • Cell Differentiation
  • Cell Line, Tumor
  • Female
  • Hypoxia, Brain / metabolism*
  • Hypoxia-Ischemia, Brain / metabolism*
  • Insulin-Like Growth Factor I / metabolism*
  • Male
  • Neurons / metabolism
  • Protein Isoforms / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Time Factors

Substances

  • Protein Isoforms
  • RNA, Messenger
  • insulin-like growth factor-1, rat
  • Insulin-Like Growth Factor I