Elsevier

Brain Research

Volume 804, Issue 1, 31 August 1998, Pages 79-86
Brain Research

Research report
Distribution and levels of insulin-like growth factor I mRNA across the life span in the Brown Norway×Fischer 344 rat brain

https://doi.org/10.1016/S0006-8993(98)00645-3Get rights and content

Abstract

Previous studies have reported changes in insulin-like growth factor I (IGF-I) mRNA expression during early postnatal development of the rat brain. Although changes in IGF-I gene expression have been documented in a wide range of central nervous system structures during early development and investigated in the hippocampus during aging, no study has compared changes in IGF-I gene expression in different brain regions across the life span. The present study assessed the distribution of IGF-I gene expression using in situ hybridization in rats aged 2–30 months. Dot blots were used as a quantitative assessment of cortical IGF-I mRNA. Results indicate that both the distribution and levels of brain IGF-I mRNA do not change significantly between 2 and 30 months of age in the rat. However, in spite of relatively constant levels of mRNA, other studies from our laboratory have demonstrated that cortical IGF-I protein levels decrease 36.6% between 11 and 32 months of age, suggesting that IGF-I function is decreased with increasing age.

Introduction

Previous studies have provided convincing evidence that neuronal expression of insulin-like growth factor-I (IGF-I) occurs throughout development and continues into adulthood. During early postnatal development, IGF-I mRNA has been shown to be transiently present in the large projection neurons of the sensory and cerebellar systems, Purkinje cells of the cerebellar cortex, and interneurons of the hippocampus and neocortex [3]. In the young adult brain, IGF-I gene expression has been reported in the olfactory bulb, hippocampus, hypothalamus, cerebellum, striatum, and neocortex 3, 14, 23, 35, 44, 45, 46. Although the specific actions of IGF-I during these different periods are largely unknown, this trophic factor has been shown to have a number of actions in both neurons and glia. For example, among other roles, IGF-I has been shown to induce neurite outgrowth 8, 33, reduce neuronal programmed cell death [20], promote synapse maintenance [7], stimulate DNA and RNA synthesis [19], regulate neuronal calcium [9]and acetylcholine release 1, 29, and induce oligodendrocyte proliferation, differentiation, and myelin production 27, 28, 37, 38, 43. The presence of IGF-I gene expression during development and adulthood and the known trophic actions of IGF-I are consistent with an integral role for IGF-I in the developing brain as well as in the adult and aging brain.

Trophic factors, such as NGF 13, 24, 25, 36, have been shown to mediate a number of functional and morphological changes during brain aging. IGF-I also has been shown to mediate specific age-related changes in the brain. Replacement of IGF-I in aged animals has been shown to improve performance on both working and reference memory tasks [26]. In addition, the normal age-related decrease in the number of hippocampal N-methyl-d-aspartate (NMDA) receptors, which have an important role in synaptic plasticity, is reversed following IGF-I administration [2]. Furthermore, plasma levels of IGF-I decrease with age 5, 12, 13as does IGF-I mRNA in a variety of tissues [30], suggesting an important role for IGF-I in functional changes that occur in the aging brain.

Despite the numerous actions of IGF-I within the central nervous system and its ability to improve memory and reverse NMDA receptor changes in aged animals, no study has compared IGF-I gene expression in different brain regions across the life span. Therefore, the goal of the present study was to investigate age-related changes in brain IGF-I mRNA.

Section snippets

Animals

Three groups of Fischer 344×Brown Norway rats, young (2–12 months), middle-aged (20–24 months) and old (30–32 months), were obtained from the National Center for Toxicological Research (NCTR) and maintained in a specific pathogen-free facility on a 12:12 light:dark cycle in a climate-controlled room. Food (Prolab Rat/Mouse/Hamster 3000 Formula, PMI Feeds) and water were available ad libitum. The animal facility at the Wake Forest University School of Medicine is fully accredited by the American

Results

In situ hybridization revealed a consistent pattern of IGF-I mRNA expression in the brain at the seven time points examined: 2, 4, 6, 8, 10, 20, and 30 months of age. Neuronal cell groups throughout the brain consistently showed signal above background. At none of the ages examined in the present study were novel sites of IGF-I gene expression evident, nor was there clear evidence of a suppression of IGF-I gene expression in specific nuclei. Meningeal labeling was frequently observed but was

Discussion

Results of the present study indicate that IGF-I mRNA distribution and levels do not change demonstrably across the life span. Qualitative in situ hybridization revealed no apparent changes in either the distribution or levels of IGF-I mRNA among the five young ages included in our study or among the young, middle, or old age groups. Not only did we observe a nearly ubiquitous distribution of neuronal IGF-I gene expression, but we also observed that this distribution persisted across all ages

Acknowledgements

The authors would like to thank Dr. Carolyn Bondy for her help with in situ hybridization techniques, Paula Cooney for her technical support, and Sean Bennett, Brandon Poe, and Philip Thornton for their help with brain collection. This work was done in partial fulfillment of the requirements for the PhD degree in the Neuroscience program of Wake Forest University School of Medicine and was supported by 1 P01 AG 11370.

References (46)

  • M.E. Lewis et al.

    Insulin-like growth factor-I: potential for treatment of motor neuronal disorders

    Exp. Neurol.

    (1993)
  • X. Liu et al.

    Astrocytes express insulin-like growth factor-I (IGF-I) and its binding protein, IGFBP-2, during demyelination induced by experimental autoimmune encephalomyelitis

    Mol. Cell. Neurosci.

    (1994)
  • P.K. Lund et al.

    Somatomedin-C/Insulin-like growth factor-I and insulin-like growth factor II mRNAs in rat fetal and adult tissues

    J. Biol. Chem.

    (1986)
  • L. Nilsson et al.

    Insulin-like growth factor I stimulates the release of acetylcholine from rat cortical slices

    Neurosci. Lett.

    (1988)
  • S.I. Rattan

    Synthesis, modifications, and turnover of proteins during aging

    Exp. Gerontol.

    (1996)
  • K.L. Stenvers et al.

    Increased expression of type I insulin-like growth factor receptor messenger RNA in rat hippocampal formation is associated with aging and behavioral impairment

    Neuroscience

    (1996)
  • F. Yamaguchi et al.

    Insulin-like growth factor I (IGFI) distribution in the tissue and extracellular compartment in different regions of the brain

    Brain Res.

    (1990)
  • S.A. Bennett et al.

    Insulin-like growth factor-I (IGF-I) regulates NMDAR1 in the hippocampus of aged animals

    Soc. Neurosci. Abstr.

    (1997)
  • C.A. Bondy

    Transient IGF-I gene expression during the maturation of functionally related central projection neurons

    J. Neurosci.

    (1991)
  • C.R. Breese et al.

    Influence of age and long-term dietary restriction on plasma insulin-like growth factor-1 (IGF-I), IGF-I gene expression, and IGF-I binding proteins

    J. Gerontol.

    (1991)
  • J.K. Brunso-Bechtold et al.

    Insulin-like growth factor-I (IGF-I) gene expression in brain vasculature: influence of age

    Soc. Neurosci. Abstr.

    (1996)
  • P. Caroni et al.

    The downregulation of growth-associated proteins in motoneurons at the onset of synapse elimination is controlled by muscle activity and IGF-I

    J. Neurosci.

    (1992)
  • P. Caroni et al.

    Nerve sprouting in innervated adult skeletal muscle induced by exposure to elevated levels of insulin-like growth factors

    J. Cell Biol.

    (1990)
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