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

Area of Science:

• Neuroscience
• Molecular Biology
• Cellular Biology

Background:

• Insulin-like growth factor 1 receptor (IGF1R) signaling is crucial for central nervous system functions, including neurogenesis, synaptic plasticity, and cognition.
• Understanding IGF1R's role in brain homeostasis is vital for addressing neurological disorders.

Purpose of the Study:

• To investigate the impact of IGF1R deficiency on brain signaling pathways, mitochondrial function, and oxidative stress.
• To characterize the consequences of conditional IGF1R deletion in the adult male mouse brain.

Main Methods:

• Conditional deletion of the Igf1r gene in 13-week-old UBC-CreERT2; Igf1r male mice.
• Analysis of PI3K/Akt and MAPK/ERK1/2 signaling pathways, tau protein levels, and caspase activity.
• Assessment of mitochondrial dynamics, respiratory chain complex activity, and oxidative stress markers (NRF2, H2O2, aconitase).

Main Results:

• IGF1R deficiency led to decreased brain weight and altered PI3K/Akt and MAPK/ERK1/2 signaling.
• Increased phosphorylated tau and altered GSK3β phosphorylation were observed, without changes in caspases 3 and 9.
• Mitochondrial dysfunction, increased oxidative stress (decreased NRF2, aconitase; increased H2O2), and impaired redox homeostasis were evident.

Conclusions:

• IGF1R plays a complex role in mediating brain signaling responses.
• IGF1R deficiency negatively impacts brain cell homeostasis and survival by disrupting mitochondrial function and redox balance.