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The neurobiology of insulin-like growth factor I: From neuroprotection to modulation of brain states

Molecular Psychiatry volume 28, pages 3220–3230 (2023)Cite this article

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Abstract

After decades of research in the neurobiology of IGF-I, its role as a prototypical neurotrophic factor is undisputed. However, many of its actions in the adult brain indicate that this growth factor is not only involved in brain development or in the response to injury. Following a three-layer assessment of its role in the central nervous system, we consider that at the cellular level, IGF-I is indeed a bona fide neurotrophic factor, modulating along ontogeny the generation and function of all the major types of brain cells, contributing to sculpt brain architecture and adaptive responses to damage. At the circuit level, IGF-I modulates neuronal excitability and synaptic plasticity at multiple sites, whereas at the system level, IGF-I intervenes in energy allocation, proteostasis, circadian cycles, mood, and cognition. Local and peripheral sources of brain IGF-I input contribute to a spatially restricted, compartmentalized, and timed modulation of brain activity. To better define these variety of actions, we consider IGF-I a modulator of brain states. This definition aims to reconcile all aspects of IGF-I neurobiology, and may provide a new conceptual framework in the design of future research on the actions of this multitasking neuromodulator in the brain.

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Fig. 1: Multilayered organization of IGF-I actions in the adult brain supporting well-being states.
Fig. 2: Pleiotropy of IGF-I in the brain.
Fig. 3: Neuroprotection by IGF-I.
Fig. 4: Modulation of brain states by IGF-I.

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Acknowledgements

We thank past members of the lab for their contributions and long-term funding support from Ciberned and the Spanish Ministerio de Ciencia e Innovación.

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Authors and Affiliations

  1. Department of Anatomy, Histology and Neurosciences, Universidad Autónoma de Madrid, Madrid, Spain

    A. Nuñez & D. Fernandez de Sevilla

  2. Achucarro Basque Center for Neuroscience, Leioa, Spain

    J. Zegarra-Valdivia & I. Torres Aleman

  3. CIBERNED, Madrid, Spain

    J. Zegarra-Valdivia, J. Pignatelli & I. Torres Aleman

  4. Universidad Señor de Sipán, Chiclayo, Perú

    J. Zegarra-Valdivia

  5. Cajal Institute (CSIC), Madrid, Spain

    J. Pignatelli

  6. Ikerbasque Science Foundation, Bilbao, Spain

    I. Torres Aleman

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AN, JZ-V, DFdeS, and JP designed and performed experiments commented in the text and reviewed the manuscript. ITA designed all the studies and wrote the manuscript.

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Nuñez, A., Zegarra-Valdivia, J., Fernandez de Sevilla, D. et al. The neurobiology of insulin-like growth factor I: From neuroprotection to modulation of brain states. Mol Psychiatry 28, 3220–3230 (2023). https://doi.org/10.1038/s41380-023-02136-6

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