Please use this identifier to cite or link to this item: http://hdl.handle.net/10316/103761
Title: IGF1R Deficiency Modulates Brain Signaling Pathways and Disturbs Mitochondria and Redox Homeostasis
Authors: Cardoso, Susana 
López, Icíar P.
Piñeiro-Hermida, Sergio
Pichel, José G.
Moreira, Paula I. 
Keywords: brain; insulin-like growth factor type 1 receptor; IGF1R-mediated signaling; mitochondria; redox balance; UBC-CreERT2; Igf1rfl/fl; IGF1R-deficient mice
Issue Date: 6-Feb-2021
Publisher: MDPI AG
Project: CENTRO-01-0145-FEDER-000012 
project PEst-C/SAU/LA0001/ 2013-2014 
UIDB/04539/2020 
Spanish Government (MICINN, PGC2018-097397-B-I00) 
Fundación Rioja Salud (Gobierno de La Rioja, 6FRSABC006) 
Serial title, monograph or event: Biomedicines
Volume: 9
Issue: 2
Abstract: 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.
URI: http://hdl.handle.net/10316/103761
ISSN: 2227-9059
DOI: 10.3390/biomedicines9020158
Rights: openAccess
Appears in Collections:FMUC Medicina - Artigos em Revistas Internacionais
I&D CIBB - Artigos em Revistas Internacionais
IIIUC - Artigos em Revistas Internacionais
I&D CNC - Artigos em Revistas Internacionais

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