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IGF Receptors in the Adult Brain

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IGFs:Local Repair and Survival Factors Throughout Life Span

Part of the book series: Research and Perspectives in Endocrine Interactions ((RPEI))

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Abstract

IGF-I action in the brain is not limited to its growth-promoting effects during fetal and neonatal development. Significant effects of IGF-I in the adult brain have been demonstrated in various contexts. The potent neuroprotective action of IGF was discovered in vitro and has been confirmed in vivo. The proposed mechanisms of IGF-I neuroprotection depend on age, and very interesting implications of IGF signaling in neurodegeneration, notably in amyotrophic lateral sclerosis and Alzheimer's disease, have been observed. The rescue of neurons following IGF-I administration has been extensively studied in rodent models in which a cerebrovascular accident is caused by experimental ischemia/hypoxia. Discrepancies have arisen in the effects of IGF-I observed in vivo, possibly reflecting the different actions of exogenous and endogenous IGF-I. Further studies are needed to elucidate the intracellular mechanisms of neuronal death following hypoxia/ischemia and the role of IGF-I in this process. Growing evidence demonstrates the selective action of IGF-I on glial cells. However, few experimental models can address the specific roles of astrocytes and microglia in the neuronal rescue mediated by IGF signaling. Endothelial cells also respond to IGF-I, possibly mediating neuroprotective effects of IGF-I through the control of edema following CNS damage. Recent studies on longevity and aging suggest that decreased insulin/insulin-like signaling increases life span and survival. Similarly, caloric restriction reduces IGF-I levels in the circulation and in the brain, at the same time increasing the longevity of the organism. Paradoxically, excess IGF-I promotes neuronal survival in the brain and reduces the longevity of the organism.

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  1. Inserm et Université Pierre et Marie Curie - UMR 893, Hôpital Saint-Antoine, Bât. Kourilsky, 184 rue du Faubourg Saint-Antoine, 75012, Paris, France

    Martin Holzenberger

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  1. Carlos De Magalhaes Filho
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  2. Martin Holzenberger
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Correspondence to Martin Holzenberger .

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  1. Chapel Hill, University of North Carolina, Burnett-Womack Hall 8024, Chapel Hill, 27599-7170, U.S.A.

    David Clemmons

  2. Lab. Endocrine Physiology, National Inst. Med. Research, The Ridgeway, London, NW7 1AA, United Kingdom

    Iain C.A.F. Robinson

  3. Recherche Therapeutique, Fondation IPSEN pour la, quai George Gorse 65, Boulogne Billancourt Cedex, 92650, France

    Yves Christen

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De Magalhaes Filho, C., Holzenberger, M. (2010). IGF Receptors in the Adult Brain. In: Clemmons, D., Robinson, I., Christen, Y. (eds) IGFs:Local Repair and Survival Factors Throughout Life Span. Research and Perspectives in Endocrine Interactions. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-04302-4_10

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