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Article

IGF1R Deficiency Modulates Brain Signaling Pathways and Disturbs Mitochondria and Redox Homeostasis

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CNC—Center for Neuroscience and Cell Biology, University of Coimbra, 3004–504 Coimbra, Portugal
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IIIUC—Institute for Interdisciplinary Research, University of Coimbra, 3030-789 Coimbra, Portugal
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CIBB—Center for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-504 Coimbra, Portugal
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Lung Cancer and Respiratory Diseases Unit (CIBIR), Fundación Rioja Salud, 26006 Logroño, Spain
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Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre (CNIO), 28029 Madrid, Spain
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Biomedical Research Networking Center in Respiratory Diseases (CIBERES), ISCIII, 28029 Madrid, Spain
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Institute of Physiology, Faculty of Medicine, University of Coimbra, 3004-517 Coimbra, Portugal
*
Authors to whom correspondence should be addressed.
Academic Editor: David R. Wallace
Biomedicines 2021, 9(2), 158; https://doi.org/10.3390/biomedicines9020158
Received: 22 December 2020 / Revised: 31 January 2021 / Accepted: 3 February 2021 / Published: 6 February 2021
(This article belongs to the Special Issue Mitochondria and Brain Disease)
Insulin-like growth factor 1 receptor (IGF1R)-mediated signaling pathways modulate important neurophysiological aspects in the central nervous system, including neurogenesis, synaptic plasticity and complex cognitive functions. In the present study, we intended to characterize the impact of IGF1R deficiency in the brain, focusing on PI3K/Akt and MAPK/ERK1/2 signaling pathways and mitochondria-related parameters. For this purpose, we used 13-week-old UBC-CreERT2; Igf1rfl/fl male mice in which Igf1r was conditionally deleted. IGF1R deficiency caused a decrease in brain weight as well as the activation of the IR/PI3K/Akt and inhibition of the MAPK/ERK1/2/CREB signaling pathways. Despite no alterations in the activity of caspases 3 and 9, a significant alteration in phosphorylated GSK3β and an increase in phosphorylated Tau protein levels were observed. In addition, significant disturbances in mitochondrial dynamics and content and altered activity of the mitochondrial respiratory chain complexes were noticed. An increase in oxidative stress, characterized by decreased nuclear factor E2-related factor 2 (NRF2) protein levels and aconitase activity and increased H2O2 levels were also found in the brain of IGF1R-deficient mice. Overall, our observations confirm the complexity of IGF1R in mediating brain signaling responses and suggest that its deficiency negatively impacts brain cells homeostasis and survival by affecting mitochondria and redox homeostasis. View Full-Text
Keywords: brain; insulin-like growth factor type 1 receptor; IGF1R-mediated signaling; mitochondria; redox balance; UBC-CreERT2; Igf1rfl/fl; IGF1R-deficient mice brain; insulin-like growth factor type 1 receptor; IGF1R-mediated signaling; mitochondria; redox balance; UBC-CreERT2; Igf1rfl/fl; IGF1R-deficient mice
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MDPI and ACS Style

Cardoso, S.; López, I.P.; Piñeiro-Hermida, S.; Pichel, J.G.; Moreira, P.I. IGF1R Deficiency Modulates Brain Signaling Pathways and Disturbs Mitochondria and Redox Homeostasis. Biomedicines 2021, 9, 158. https://doi.org/10.3390/biomedicines9020158

AMA Style

Cardoso S, López IP, Piñeiro-Hermida S, Pichel JG, Moreira PI. IGF1R Deficiency Modulates Brain Signaling Pathways and Disturbs Mitochondria and Redox Homeostasis. Biomedicines. 2021; 9(2):158. https://doi.org/10.3390/biomedicines9020158

Chicago/Turabian Style

Cardoso, Susana, Icíar P. López, Sergio Piñeiro-Hermida, José G. Pichel, and Paula I. Moreira 2021. "IGF1R Deficiency Modulates Brain Signaling Pathways and Disturbs Mitochondria and Redox Homeostasis" Biomedicines 9, no. 2: 158. https://doi.org/10.3390/biomedicines9020158

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