title: Protective effects of insulin-like growth factor-I on the somatostatinergic system in the temporal cortex of beta-amyloid-treated rats.
abstract: Insulin-like growth factor-I (IGF-I) has protective effects against beta-amyloid (Abeta)-induced neuronal cell death. Because alterations of the somatostatinergic system have been described in Alzheimer's disease, we investigated the effects of the Abeta peptide and the possible protective role of IGF-I on the somatostatinergic system of the rat temporal cortex and on cell death and phosphorylated (p)-Akt levels in this area. Abeta25-35 was administered intracerebroventricularly to male rats via an osmotic minipump over 14 days (300 pmol/day). Another group received a subcutaneous IGF-I infusion (50 microg/kg/day), concomitant with Abeta25-35 administration, whereas a third group received IGF-I alone. Abeta25-35 significantly decreased the somatostatin (SRIF)-like immunoreactive content and the SRIF receptor density, as a result of a decrease in the levels of the SRIF receptor subtype 2. The inhibitory effect of SRIF on adenylyl cyclase activity was significantly lower after Abeta25-35 infusion, whereas the levels of the inhibitory G protein subunit Gialpha1, Gialpha2 or Gialpha3 were unaltered. Cell death was increased and p-Akt levels decreased in Abeta25-35-treated animals. IGF-I administration increased immunoreactive IGF-I levels in the temporal cortex and restored all parameters affected by Abeta25-35 to baseline values. These findings suggest that IGF-I prevents the deleterious effect of Abeta25-35 on the somatostatinergic system.
authors.affiliation: Research Laboratory, Universidad Autónoma, Hospital Infantil Universitario Niño Jesús, Avda. Menéndez Pelayo 65, E-28009 Madrid, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Aguado-Llera
authors.forename: E
authors.initials: E
authors.lastname: Arilla-Ferreiro
authors.forename: A
authors.initials: A
authors.lastname: Campos-Barros
authors.forename: L
authors.initials: L
authors.lastname: Puebla-Jiménez
authors.forename: V
authors.initials: V
authors.lastname: Barrios
mesh_terms: D000544:Alzheimer Disease / Q000139:chemically induced / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D004333:Drug Administration Routes; D004336:Drug Antagonism; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000633:toxicity; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D017208:Rats, Wistar; D017481:Receptors, Somatostatin / Q000187:drug effects / Q000378:metabolism; D013004:Somatostatin / Q000378:metabolism*; D013702:Temporal Lobe / Q000187:drug effects* / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D011518:Proto-Oncogene Proteins; D017481:Receptors, Somatostatin; C074636:amyloid beta-protein (25-35); D013004:Somatostatin; D007334:Insulin-Like Growth Factor I; C494920:Akt1 protein, rat; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; D019206:GTP-Binding Protein alpha Subunits, Gi-Go