title: 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.
abstract: 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.
authors.affiliation: Neuropsychiatric Genetics Research Group, Department of Psychiatry, Trinity College Dublin, St. James Hospital, Dublin 8, Ireland.
authors.forename: Aiden P
authors.initials: AP
authors.lastname: Corvin
authors.forename: Ines
authors.initials: I
authors.lastname: Molinos
authors.forename: Graham
authors.initials: G
authors.lastname: Little
authors.forename: Gary
authors.initials: G
authors.lastname: Donohoe
authors.forename: Michael
authors.initials: M
authors.lastname: Gill
authors.forename: Derek W
authors.initials: DW
authors.lastname: Morris
authors.forename: Daniela
authors.initials: D
authors.lastname: Tropea
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000494:pharmacology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D061251:Primary Cell Culture; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction; D013569:Synapses / Q000378:metabolism
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases; D017526:Receptor, IGF Type 1; D020928:Mitogen-Activated Protein Kinases