The Protective Effects of IGF-I against β-Amyloid-related Downregulation of Hippocampal Somatostatinergic System Involve Activation of Akt and Protein Kinase A

Publication date: 15 March 2018 Source:Neuroscience, Volume 374 Author(s): David Aguado-Llera, Sandra Canelles, Laura M. Frago, Julie A. Chowen, Jesús Argente, Eduardo Arilla, Vicente Barrios Somatostatin (SRIF), a neuropeptide highly distributed in the hippocampus and involved in learning and memory, is markedly reduced in the brain of Alzheimer’s disease patients. The effects of insulin-like growth factor-I (IGF-I) against β amyloid (Aβ)-induced neuronal death and associated cognitive disorders have been extensively reported in experimental models of this disease. Here, we examined the effect of IGF-I on the hippocampal somatostatinergic system in Aβ-treated rats and the molecular mechanisms associated with changes in this peptidergic system. Intracerebroventricular Aβ25-35 administration during 14 days (300 pmol/day) to male rats increased Aβ25-35 levels and cell death and markedly reduced SRIF and SRIF receptor 2 levels in the hippocampus. These deleterious effects were associated with reduced Akt and cAMP response element-binding protein (CREB) phosphorylation and activation of c-Jun N-terminal kinase (JNK). Subcutaneous IGF-I co-administration (50 µg/kg/day) reduced hippocampal Aβ25-35 levels, cell death and JNK activation. In addition, IGF-I prevented the reduction in the components of the somatostatinergic system affected by Aβ infusion. Its co-administration also augmented protein kinase A (PKA) activity, as well as Akt and CREB phosphorylat...

Source: Neuroscience - February 10, 2018 Category: Neuroscience Source Type: research