Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8840927 | Neuroscience | 2018 | 15 Pages |
Abstract
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 14â¯days (300â¯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 (50â¯Âµg/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 phosphorylation. These results suggest that IGF-I co-administration may have protective effects on the hippocampal somatostatinergic system against Aβ insult through up-regulation of PKA activity and Akt and CREB phosphorylation.
Keywords
CREBSRIFIRS1NT-3GSK3βIBA1TTBSRIAintracerebroventricularICVNeuNCCKpKaIGF-INPYVIPSSTJnkAβHRPPI3KBDNFc-Jun N-terminal kinaseβ-Amyloidadenylyl cyclaseinsulin-degrading enzymeAktγ-aminobutyric acidinsulin-like growth factor IinterleukinIDEBeta-amyloidAlzheimer’s diseaseradioimmunoassayinsulin receptor substrate 1SomatostatinBrain-derived neurotrophic factorphosphatidylinositol-3 kinasephosphorylated ionized calcium-binding adaptor molecule 1neurotrophin-3neuronal nucleiHippocampusHorseradish peroxidaseCRE-binding proteinGlial fibrillary acidic proteinprotein kinase Aprotein kinase Bvasoactive intestinal peptideGABAGlycogen synthase kinase 3βNeuropeptide Y
Related Topics
Life Sciences
Neuroscience
Neuroscience (General)
Authors
David Aguado-Llera, Sandra Canelles, Laura M. Frago, Julie A. Chowen, Jesús Argente, Eduardo Arilla, Vicente Barrios,