Research reportDistribution and levels of insulin-like growth factor I mRNA across the life span in the Brown Norway×Fischer 344 rat brain
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)
- et al.
Insulin-like growth factor-I (somatomedin-C) receptors in the rat brain: distribution and interaction with the hippocampal cholinergic system
Brain Res.
(1989) - et al.
The cellular pattern of type-I IGF receptor expression during maturation of the rat brain: comparison with IGF-I and IGF-II
Neuroscience
(1992) - et al.
IGF-I and IGF-II protect cultured hippocampal and septal neurons against calcium-mediated hypoglycemic damage
J. Neurosci.
(1992) - et al.
Insulin-like growth factor (IGF)-I stimulation of protein synthesis is attenuated in cortex of aging rat brains
Neuroscience
(1995) - et al.
Distribution and levels of [125I]IGF-I, [125I]IGF-II, and [125I]Insulin receptor binding sites in the hippocampus of aged memory-unimpaired and -impaired rats
Neuroscience
(1997) - et al.
Human blood-brain barrier insulin-like growth factor receptor
Metab.: Clin. and Exp.
(1988) - et al.
Effect of rat age on serum levels of growth hormone and somatomedins
Mech. Ageing Dev.
(1981) - et al.
Localization of insulin-like growth factor I (IGF-I)-like immunoreactivity in the developing and adult rat brain
Brain Res.
(1991) - et al.
Expression of insulin-like growth factor-I and related peptides during motoneuron regeneration
Exp. Neurobiol.
(1994) - et al.
Insulin-like growth factor I (IGF-I) stimulates DNA synthesis in fetal rat brain cell cultures
Dev. Brain Res.
(1983)