Localization of the insulin-like growth factor I receptor in the cerebellum and hypothalamus of adult rats: an electron microscopic study
Purchase on Springer.com
$39.95 / €34.95 / £29.95*
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.
Insulin-like growth factor I (IGF-I) is an important modulator of cell growth and plasticity in the CNS. Expression of the IGF-I receptor mRNA in brain peaks at times of active cell development perinatally and remains detectable, albeit at lower levels, in the adult. While both autoradiographic and in situ hybridization studies show a wide and specific distribution of IGF-I receptor throughout the adult rat brain, nothing is yet known about its subcellular localization, a critical issue that will help clarify the biological role of this trophic factor in the adult brain. The present study describes the subcellular localization of IGF-I receptor immunoreactivity in the cerebellar cortex and the hypothalamic arcuate nucleus by using electron microscopic immunocytochemistry. In the cerebellum, IGF-I receptor immunoreactivity is present postsynaptically in the dendrites and soma of the Purkinje cell and presynaptically in axon terminals impinging upon the Purkinje cell soma, as well as in mossy fibre rosettes in the cerebellar glomeruli. Neurons in the mediobasal hypothalamus also contain IGF-I receptors located pre- and postsynaptically. Endothelial cells, astroglial end-feet surrounding micro vessels throughout all the brain parenchyma, tanycytes of the third ventricle and oligodendrocytes in the cerebellar white matter are also rich in IGF-I receptors. These results strongly support previous observations that IGF-I is a neuromodulator in the adult brain, probably acting as both a pre- and a postsynaptic messenger. They also suggest that glial cells may be involved in the actions of IGF-I in the adult brain.
- Aguado, F., Sanchez-Franco, F., Cacicedo, L., Fernandez, T., Rodrigo, J. & Martinezmurillo, R. (1992) Subcellular localization of insulinlike growth factor I (IGF-I) in Purkinje cells of the adult rat: an immunocytochemical study. Neuroscience Letters 135, 171–4.
- Aguado, F., Rodrigo, J., Cacicedo, L. & Mellstrom, B. (1993) Distribution of insulin-like growth factor-I receptor mRNA in rat brain. Regulation in the hypothalamo–neurohypophysial system. Journal of Molecular Endocrinology 11, 231–9.
- Andersson, I. K., Edwall, D., Norstedt, G., Rozell, B., Skottner, A. & Hansson, H. A. (1988) Differing expression of insulin-like growth factor I in the developing and in the adult rat cerebellum. Acta Physiologica Scandinavica 132, 167–73.
- Araujo, D. M., Lapchak, P. A., Collier, B., Chabot, J. G. & Quirion, R. (1989) Insulin-like growth factor-I (somatomedin-C) receptors in the rat brain: Distribution and interaction with the hippocampal cholinergic systems. Brain Research 484, 130–8.
- Auletta, M., Nielsen, F. C. & Gammeltoft, S. (1992) Receptor-mediated endocytosis and degradation of insulin-like growth factor I and II in neonatal rat astrocytes. Journal of Neuroscience Research 31, 14–20.
- Bach, M. A., Shen-Orr, Z., Lowe, W. L., Roberts, C. T. & LeRoith, D. (1991) Insulin-like growth factor I mRNA levels are developmentally regulated in specific regions of the rat brain. Molecular Brain Research 10, 43–8.
- Bartlett, W. P., Li, X. S., Williams, M. & Benkovic, S. (1991) Localization of insulin-like growth factor-I mRNA in murine central nervous system during postnatal development. Developmental Biology 147, 239–50.
- Beck, K. D., Powell-Braxton, L., Widmer, H. R., Valverde, J. & Hefti, F. (1995) Igf1 gene disruption results in reduced brain size, CNS hypomyelination, and loss of hippocampal granule and striatal parvalbumin-containing neurons. Neuron 14, 717–30. CrossRef
- Becker, K., Stegenga, S. & Conway, S. (1995) Role of insulin-like growth factor I in regulating growth hormone release and feedback in the male rate. Neuroendocrinology 61, 573–83.
- Berelowitz, M., Szabo, M., Frohman, L. A., Firestone, S., Chu, L. & Hintz, R. L. (1981) Somatomedin C mediates growth hormone negative feedback by effects on both the hypothalamus and the pituitary. Science 212, 1279–81.
- Bondy, C. A. (1991) Transient IGF-I gene expression during the maturation of functionally related central projecting neurons. Journal of Neuroscience 11, 3442–55.
- Bondy, C. & Lee, W. H. (1993) Correlation between insulin-like growth factor (IGF)-binding protein 5 and IGF-I gene expression during brain development. Journal of Neuroscience 13, 5092–104.
- Bondy, C., Werner, H., Roberts, C. T. & LeRoith, D. (1992) Cellular pattern of type-I insulin-like growth factor receptor gene expression during maturation of the rat brain: Comparison with insulin-like growth factors I and II. Neuroscience 46, 909–23.
- Bourguignon, J. P., Gerard, A., Alvarez Gonzalez M. L. & Franchimont, P. (1993) Acute suppression of gonadotrophin-releasing hormone secretion by insulin-like growth factor I and subproducts: an age dependent endocrine effect. Neuroendocrinology 58, 525–30.
- Castro-Alamancos, M. A. & Torres-Aleman, I. (1993) Long-term depression of glutamate-induced gamma-aminobutyric acid release in cerebellum by insulin-like growth factor I. Proceedings of the National Academy of Sciences (USA) 90, 7386–90.
- Castro-Alamancos, M. A. & Torres-Aleman, I. (1994) Learning of the conditioned eye-blink response is impaired by an antisense insulin-like growth factor I oligonucleotide. Proceedings of the National Academy of Sciences (USA) 91, 10203–7.
- DeFelipe, J. & Fairén, A. (1993) A simple and reliable method for correlative light and electron microscopic studies. Journal of Histochemistry and Cytochemistry 41, 769–72.
- De Pablo, F. & De la Rosa, E. J. (1995) The developing CNS: a scenario for the action of proinsulin, insulin and insulin-like growth factors. Trends in Neuroscience 18, 143–50.
- DueÑas, M., Luquin, S., Chowen, J. A., Torresaleman, I., Naftolin, F. & Garcia-Segura, L. M. (1994) Gonadal hormone regulation of insulin-like growth factor-I-like immunoreactivity in hypothalamic astroglia of developing and adult rats. Neuroendocrinology 59, 528–38.
- DueÑas, M., Torres-Aleman, I., Naftolin, F. & Garcia-Segura, L. M. (1996) Interaction of insulin-like growth factor-I and estradiol signaling pathways on hypothalamic neuronal differentiation. Neuroscience 74, 531–9.
- Fernandez-Galaz, M. C., Torres-Aleman, I. & Garcia-Segura, L. M. (1996) Endocrine-dependent accumulation of IGF-I by hypothalamic glia. Neuro-Report 8, 373–7.
- Garcia-Segura, L. M., Perez, J., Pons, S. Rejas, M. T. & Torres-Aleman, I. (1991) Localization of insulin-like growth factor I (IGF-I)-like immunoreactivity in the rat brain. Brain Research 560, 167–74.
- Garcia-Segura, L. M., Chowen, J. A. & Naftolin, F. (1996) Endocrine glia: Roles of glial cells in the brain actions of steroid and thyroid hormones and in the regulation of hormone secretion. Frontiers in Neuroendocrinology 17, 180–211.
- Hawker, J. R. & Granger, H. J. (1992) Internalized basic fibroblast growth factor translocates to nuclei of venular endothelial cells. American Journal of Physiology 262, H1525–37.
- Hiney, J. J., Ojeda, S. R. & Les Dees, W. (1991) Insulin-like growth factor I: A possible metabolic signal involved in the regulation of female puberty. Neuroendocrinology 54, 420–3.
- Hiney, J. K., Srivastava, V., Nyberg, C. L., Ojeda, S. R. & Les Dees, W. (1996) Insulin-like growth factor I of peripheral origin acts centrally to accelerate the initiation of female puberty. Endocrinology 137, 3717–28.
- HÖkfelt, T. (1991) Neuropeptides in perspective: the last ten years. Neuron 7, 867–79. CrossRef
- Jans, D. A. (1994) Nuclear signaling pathways for polypeptide ligands and their membrane receptors? FASEB Journal 8, 841–7.
- Kar, S., Chabot, J. G. & Quirion, R. (1993) Quantitative autoradiographic localization of [125I]insulin-like growth factor I, [125I]insulin-like growth factor II, and [125I]insulin receptor binding sites in developing and adult rat brain. Journal of Comparative Neurology 333, 375–97.
- Kim, S. J. & Kahn, C. R. (1993) Insulin induces rapid accumulation of insulin receptors and increases tyrosine kinase activity in the nucleus of cultured adipocytes. Journal of Cell Physiology 157, 217–28.
- Komoly, S., Hudson, L. D., Webster, H. D. & Bondy, C. A. (1992) Insulin-like growth factor I gene expression is induced in astrocytes during experimental demyelination. Proceedings of the National Academy of Sciences (USA) 89, 1894–8.
- Laudron, P. M. (1994) From receptor internalization to nuclear translocation. New targets for long-term pharmacology. Biochemical Pharmacology 13, 3–13.
- Lee, W. H., Javedan, S. & Bondy, C. A. (1992) Coordinate expression of insulin-like growth factor system components by neurons and neuroglia during retinal and cerebellar development. Journal of Neuroscience 12, 4737–44.
- Leranth, C., Shanabrough, M. & Naftolin, F. (1991) Estrogen induces ultrastructural changes in progesterone receptor-containing GABA neurons of the primate hypothalamus. Neuroendocrinology 54, 571–9.
- Lesniak, M. A., Hill, J. M., Kiess, W., Rojeski, M., Pert, C. B. & Roth, J. (1988) Receptors for insulin-like growth factors I and II: Autoradiographic localization in rat brain and comparison to receptors for insulin. Endocrinology 123, 2089–99.
- Llano, I., Leresche, N. & MARTY, A. (1991) Calcium entry increases the sensitivity of cerebellar Purkinje cells to applied GABA and decreases inhibitory synaptic currents. Neuron 6, 565–74.
- Lobie, P. E., Mertani, H., Morel, G., Moralesbustos, O., Norstedt, G. & Waters, M. J. (1994) Receptor-mediated nuclear translocation of growth hormone. Journal of Biological Chemistry 269, 21330–9.
- Ma, Y. J., Junier, M. P., Costa, M. E. & Ojeda, S. R. (1992) Transforming growth factor-a gene expression in the hypothalamus is developmentally regulated and linked to sexual maturation. Neuron 9, 657–70.
- Marks, J. K., Porte, D. & Baskin, D. G. (1991) Localization of type I insulin-like growth factor receptor messenger RNA in the adult rat brain by in situ hybridization. Molecular Endocrinology 5, 1158–68.
- Masters, B. A., Werner, H., Roberts, C. T., LeRoith, D. & Raizada, M. K. (1991) Insulin-like growth factor I (IGF-I) receptors and IGF-I action in oligodendrocytes from rat brains. Regulatory Peptides 25, 117–31.
- Moss, A. M. & Livingston, J. N. (1993) Distinct beta-subunits are present in hybrid insulin-like-growth-factor-1 receptors in the central nervous system. Biochemical Journal 294, 685–92.
- Mozell, R. L. & McMorris, F. A. (1991) Insulin-like growth factor I stimulates oligodendrocyte development and myelination in rat brain aggregate cultures. Journal of Neuroscience Research 30, 382–90.
- Nieto-Bona, M. P., Busiguina, S. & Torres-Aleman, I. (1995) Insulin-like growth factor I is an afferent trophic signal that modulates calbindin-28kD in adult Purkinje cells. Journal of Neuroscience Research 42, 371–6.
- Nilsson, L., Sara, V. R. & Nordberg, A. (1988) Insulin-like growth factor I stimulates the release of acetylcholine from rat cortical slices. Neuroscience Letters 88, 221–6.
- Ocrant, I., Fay, C. T. & Parmelee, J. T. (1990) Characterization of insulin-like growth factor binding proteins produced in the rat central nervous system. Endocrinology 127, 1260–7.
- Pons, S., Rejas, M. T. & Torres-Aleman, I. (1991) Ontogeny of insulin-like growth factor I, its receptor, and its binding proteins in the rat hypothalamus. Developmental Brain Research 62, 169–75.
- Quiroga, S., Garofalo, R. S. & Pfenninger, K. H. (1995) Insulin-like growth factor I receptors of fetal brain are enriched in nerve growth cones and contain a b-subunit variant. Proceedings of the National Academy of Sciences (USA) 92, 4309–12.
- Rao, Y. P., Olson, M. D., Buckley, D. J. & Buckley, A. R. (1993) Nuclear co-localization of prolactin and the prolactin receptor in rat Nb2 node lymphoma cells. Endocrinology 133, 3062–5.
- Rao, Y. P., Buckley, D. J., Olson, M. D. & Buckley, A. R. (1995) Nuclear translocation of prolactin: collaboration of tyrosine kinase and protein kinase C activation in rat Nb2 node lymphoma cells. Journal of Cell Physiology 163, 266–76.
- Reinhardt, R. R. & Bondy, C. A. (1994) Insulin-like growth factors cross the blood–brain barrier. Endocrinology 135, 1753–61.
- Rotwein, P., Burgess, S. K., Milbrandt, J. D. & Krause, J. E. (1988) Differential expression of insulin-like growth factor genes in rat central nervous system. Proceedings of the National Academy of Sciences (USA) 85, 265–9.
- Shah, N. Zhang, S., Harada, S., Smith, R. M. & Jarett, L. (1995) Electron microscopic visualization of insulin translocation into the cytoplasm and nuclei of intact H35 hepatoma cells using covalently linked nanogold–insulin. Endocrinology 136, 2825–35.
- Shemer, J., Raizada, M. K., Masters, B. A., Ota, A. & LeRoith, D. (1987) Insulin-like growth factor I receptors in neuronal and glial cells. Journal of Biological Chemistry 262, 7693–99.
- Solari, R., Smithers, N., Kennard, N., Ray, K. & Grenfell, S. (1994) Receptor mediated endocytosis and intracellular fate of interleukin 1. Biochemical Pharmacology 13, 93–101.
- Tannenbaum, G. S., Guyda, H. J. & Posner, B. I. (1983) Insulin-like growth factors: A role in growth hormone negative feedback and body weight regulation via brain. Science 220, 77–9.
- Torres-Aleman, I., Pons, S. & Arevalo, M. A. (1994) The insulin-like growth factor I system in the rat cerebellum: developmental regulation and role in neuronal survival and differentiation. Journal of Neuroscience Research 39, 117–26.
- Uchiyama, T., Kaji, H., Abe, H. & Chihara, K. (1994) Negative regulation of hypothalamic growth hormonereleasing factor messenger ribonucleic acid by growth hormone and insulin-like growth factor I. Neuroendocrinology 59, 441–50.
- Vincent, P. & Marty, A. (1993) Neighboring cerebellar Purkinje cells communicate via retrograde inhibition of common presynaptic interneurons. Neuron 11, 885–93.
- Walicke, P. A. & Baird, A. (1991) Internalization and processing of basic fibroblast growth factor by neurons and astrocytes. Journal of Neuroscience 11, 2249–58.
- Werther, G. A., Abate, M., Hogg, A., Cheesman, H., Oldfield, B., Hards, D., Hudson, P., Power, B., Freed, K. & Herington, A. C. (1990) Localization of insulin-like growth factor-I mRNA in rat brain by in situ hybridization – relationship to IGF-I receptors. Molecular Endocrinology 4, 773–8.
- Localization of the insulin-like growth factor I receptor in the cerebellum and hypothalamus of adult rats: an electron microscopic study
Journal of Neurocytology
Volume 26, Issue 7 , pp 479-490
- Cover Date
- Print ISSN
- Online ISSN
- Kluwer Academic Publishers
- Additional Links