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Sánchez-Sarasúa S, Meseguer-Beltrán M, García-Díaz C, et al. IRS1 expression in hippocampus is age-dependent and is required for mature spine maintenance and neuritogenesis. Mol Cell Neurosci. 2021;103693doi: 10.1016/j.mcn.2021.103693.
Sánchez-Sarasúa, S., Meseguer-Beltrán, M., García-Díaz, C., Beltrán-Bretones, M. T., ElMlili, N., & Sánchez-Pérez, A. M. (2021). IRS1 expression in hippocampus is age-dependent and is required for mature spine maintenance and neuritogenesis. Molecular and cellular neurosciences, 103693. https://doi.org/10.1016/j.mcn.2021.103693
Sánchez-Sarasúa, Sandra, et al. "IRS1 expression in hippocampus is age-dependent and is required for mature spine maintenance and neuritogenesis." Molecular and cellular neurosciences vol. (2021): 103693. doi: https://doi.org/10.1016/j.mcn.2021.103693
Sánchez-Sarasúa S, Meseguer-Beltrán M, García-Díaz C, Beltrán-Bretones MT, ElMlili N, Sánchez-Pérez AM. IRS1 expression in hippocampus is age-dependent and is required for mature spine maintenance and neuritogenesis. Mol Cell Neurosci. 2021 Dec 20;103693. doi: 10.1016/j.mcn.2021.103693. Epub 2021 Dec 20. PMID: 34942345.
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Mol Cell Neurosci. 2021 Dec 20;103693. doi: 10.1016/j.mcn.2021.103693. Epub 2021 Dec 20.

IRS1 expression in hippocampus is age-dependent and is required for mature spine maintenance and neuritogenesis.

Molecular and cellular neurosciences

Sandra Sánchez-Sarasúa, María Meseguer-Beltrán, Cristina García-Díaz, Maria Teresa Beltrán-Bretones, Nisrin ElMlili, Ana María Sánchez-Pérez

Affiliations

  1. Neutobiotechnology Lab, INAM, University of Jaume I, Castellon, Spain.
  2. Laboratory of Neurobiology and Health, Faculty of Sciences, University of Abdelmalek Essaadi, Tetuan, Morocco.
  3. Neutobiotechnology Lab, INAM, University of Jaume I, Castellon, Spain. Electronic address: [email protected].

PMID: 34942345 DOI: 10.1016/j.mcn.2021.103693

Abstract

Insulin and insulin-like growth factor type I (IGF-1) play prominent roles in brain activity throughout the lifespan. Insulin/IGF1 signaling starts with the activation of the intracellular insulin receptor substrates (IRS). In this work, we performed a comparative study of IRS1 and IRS2, together with the IGF1 (IGF1R) and insulin (IR) receptor expression in the hippocampus and prefrontal cortex during development. We found that IRS1 and IRS2 expression is prominent during development and declines in the aged hippocampus, contrary to IR, which increases in adulthood and aging. In contrast, IGF1R expression is unaffected by age. Expression patterns are similar in the prefrontal cortex. Neurite development occurs postnatally in the rodent hippocampus and cortex, and it declines in the mature and aged brain and is influenced by trophic factors. In our previous work, we demonstrated that knockdown of IRS1 by shRNA impairs learning and reduces synaptic plasticity in a rat model, as measured by synaptophysin puncta in axons. In this study, we report that shIRS1 alters spine maturation in adult hilar hippocampal neurons. Lastly, to understand the role of IRS1 in neuronal neurite tree, we transfect shIRS1 into primary neuronal cultures and observed that shIRS1 reduced neurite branching and neurite length. Our results demonstrate that IRS1/2 and insulin/IGF1 receptors display different age-dependent expression profiles and that IRS1 is required for spine maturation, demonstrating a novel role for IRS1 in synaptic plasticity.

Copyright © 2021. Published by Elsevier Inc.

Keywords: IGF-1; IRS expression; Insulin; Neurite branching; Prefrontal cortex; Sholl analysis; Spine morphology; hippocampus; shRNA

Conflict of interest statement

Declaration of competing interest The authors declare no conflict of interest.

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