Microglia-Derived Insulin-like Growth Factor 1 Is Critical for Neurodevelopment

Author:

Rusin Dominika1,Vahl Becirovic Lejla1ORCID,Lyszczarz Gabriela1,Krueger Martin2,Benmamar-Badel Anouk1,Vad Mathiesen Cecilie13,Sigurðardóttir Schiöth Eydís1,Lykke Lambertsen Kate145ORCID,Wlodarczyk Agnieszka14ORCID

Affiliation:

1. Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark

2. Institute for Anatomy, University of Leipzig, 04103 Leipzig, Germany

3. Neuroscience Academy Denmark, Blegdamsvej 3B, 2200 Copenhagen N, Denmark

4. Department of Clinical Research, BRIDGE—Brain Research Interdisciplinary Guided Excellence, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark

5. Department of Neurology, Odense University Hospital, 5000 Odense C, Denmark

Abstract

Insulin-like growth factor 1 (IGF-1) is a peptide hormone essential for the proper development and growth of the organism, as a complete knockout of Igf1 in mice is lethal, causing microcephaly, growth retardation and the defective development of organs. In the central nervous system, neurons and glia have been reported to express Igf1, but their relative importance for postnatal development has not yet been fully defined. In order to address this, here, we obtained mice with a microglia-specific inducible conditional knockout of Igf1. We show that the deficiency in microglial Igf1, starting in the first postnatal week, leads to body and brain growth retardation, severely impaired myelination, changes in microglia numbers, and behavioral abnormalities. These results emphasize the importance of microglial-derived Igf1 for brain development and function and open new perspectives for the investigation of the role of microglial-Igf1 in neurological diseases.

Funder

Lundbeck Foundation

Scleroseforeningen

Direktør Ejnar Jonasson, kaldet Johnsen, og Hustru’s Mindelegat

Danish Research Council

Publisher

MDPI AG

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1. CNS Resident Innate Immune Cells: Guardians of CNS Homeostasis;International Journal of Molecular Sciences;2024-04-29

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