Insulin-like growth factor 1 (IGF1) and its active peptide (1–3)IGF1 enhance the expression of synaptic markers in neuronal circuits through different cellular mechanisms

• Published in: Neuroscience letters 2012-06, Vol.520 (1), p.51-56
• Main Authors: Corvin, Aiden P., Molinos, Ines, Little, Graham, Donohoe, Gary, Gill, Michael, Morris, Derek W., Tropea, Daniela
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Biomarkers - metabolism; Cells, Cultured; Cerebral Cortex - cytology; Growth factors; Humans; Insulin-like growth factor 1; Insulin-Like Growth Factor I - biosynthesis; Insulin-Like Growth Factor I - pharmacology; Mice; Mitogen-Activated Protein Kinases - metabolism; Neurons - drug effects; Neurons - metabolism; Peptide Fragments - pharmacology; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation; Primary Cell Culture; Receptor, IGF Type 1 - metabolism; Recombinant Proteins - pharmacology; Signal Transduction; Synapses - metabolism; Synaptic transmission
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2012.05.029

► Both IGF1 and (1–3)IGF1 enhance the phosphorylation of the IGF1 receptor. ► Both IGF1 and (1–3)IGF1 enhance the expression of synapsin and PSD95. ► IGF1 and (1–3)IGF1 act through different signaling pathways. ► (1–3)IGF1 enhances the expression of endogenous IGF1. Insulin-like growth factor-1 (IGF1) and its active peptide (1–3)IGF1 modulate brain growth and plasticity and are candidate molecules for treatment of brain disorders. IGF1 N-terminal portion is naturally cleaved to generate the tri-peptide (1–3)IGF1 (glycine–praline–glutamate). IGF1 and (1–3)IGF have been proposed as treatment for neuropathologies, yet their effect on nerve cells has not been directly compared. In this study we examine the effects of IGF1 and (1–3)IGF1 in primary cortical cultures and measure the expression levels of markers for intracellular pathways and synaptic function. We find that both treatments activate the IGF1 receptor and enhance the expression of synaptic markers, however, they activate different intracellular pathways. Furthermore, (1–3)IGF1 administration increases the expression of endogenous IGF1, suggesting a direct interaction between the two molecules. The results show that the two molecules increase the expression of synaptic proteins through activating different cellular mechanisms.