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  • Review Article
  • Published:

Insulin and IGF receptor signalling in neural-stem-cell homeostasis

Nature Reviews Endocrinology volume 11, pages 161–170 (2015)Cite this article

Subjects

Key Points

  • Insulin-like growth factor I (IGF-I) and insulin-like growth factor II (IGF-II) are synthesized in the brain and their levels decline with ageing

  • IGF-I and IGF-II exert different effects on neural stem cells (NSCs)

  • IGF-I collaborates with other mitogens to enlarge the pool of neural progenitors

  • IGF-II specifically promotes NSC self-renewal and stem-cell replication through the insulin receptor isoform A

  • IGF-II does not affect NSC self-renewal through the IGF-II receptor

Abstract

Neural stem cells (NSCs) are found in two regions in the adult brain: the subgranular zone (SGZ) in the hippocampal dentate gyrus and the subventricular zone (SVZ) adjacent to the lateral ventricles. Similarly to other somatic stem cells, adult NSCs are found within specialized niches that are organized to facilitate NSC self-renewal. Alterations in stem-cell homeostasis can contribute to the consequences of neurodegenerative diseases, healthy ageing and tissue repair after damage. Insulin and the insulin-like growth factors (IGFs) function in stem-cell homeostasis across species. Studies in the mammalian central nervous system support essential roles for IGF and/or insulin signalling in NSC self-renewal, neurogenesis, cognition and sensory function through distinct ligand–receptor interactions. IGF-II is of particular interest as a result of its production by the choroid plexus and presence in cerebrospinal fluid (CSF). CSF regulates and supports the development, division and migration of cells in the adult brain and is required for NSC maintenance. In this Review, we discuss emerging data on the functions of IGF-II and IGF and/or insulin receptor signalling in the context of NSC regulation in the SVZ and SGZ. We also propose a model for IGF-II in which the choroid plexus is a major component of the NSC niche.

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Figure 1: Neurogenic regions in the adult brain.
Figure 2: Structure of the neonatal subventricular zone.
Figure 3: Proposed model for the actions of IGFs in the subventricular zone.

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Acknowledgements

The authors would like to thank S. Chidambaram for assistance with Figure 2. S.W.L. and T.L.W. acknowledge research support from the NIH (NIH-NINDS R21NS076874). A.N.Z. acknowledges research support from the NIH (NIH-NINDS F31NS065607).

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  1. Department of Neurology & Neuroscience, New Jersey Medical School, Rutgers Biomedical & Health Sciences, Cancer Centre, 205 South Orange Avenue, Newark, 07101, NJ, USA

    Amber N. Ziegler, Steven W. Levison & Teresa L. Wood

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  1. Amber N. Ziegler
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  2. Steven W. Levison
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A.N.Z., S.W.L. and T.L.W. researched data for the article, provided substantial contributions to discussions of the content, wrote the article and edited the manuscript before submission.

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Correspondence to Teresa L. Wood.

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Ziegler, A., Levison, S. & Wood, T. Insulin and IGF receptor signalling in neural-stem-cell homeostasis. Nat Rev Endocrinol 11, 161–170 (2015). https://doi.org/10.1038/nrendo.2014.208

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