RT info:eu-repo/semantics/article T1 Chronic but not acute intracerebroventricular administration of amyloid ß-peptide(25-35) decreases somatostatin content, adenylate cyclase activity, somatostatin-induced inhibition of adenylate cyclase activity, and adenylate cyclase I levels in the rat hippocampus A1 Burgos Ramos, Emma A1 Hervás Aguilar, América A1 Puebla Jiménez, Lilian A1 Boyano Adánez, María del Carmen A1 Arilla Ferreiro, Eduardo K1 Adenylate cyclase K1 Amyloid ß K1 Brain K1 Gi proteins K1 Hippocampus K1 Peptide K1 Rat K1 Bioquímica K1 Biochemistry K1 Science K1 Ciencia AB Although alterations in adenylate cyclase (AC) activity and somatostatin (SRIF) receptor density have been reported in Alzheimer's disease, the effects of amyloid β-peptide (Aβ) on these parameters in the hippocampus are unknown. Our aim was to investigate whether the peptide fragment Aβ(25–35) can affect the somatostatinergic system in the rat hippocampus. Hence, Aβ(25–35) was injected intracerebroventricularly (i.c.v.) to Wistar rats in a single dose or infused via an osmotic minipump connected to a cannula implanted in the right lateral ventricle during 14 days. The animals were decapitated 7 or 14 days after the single injection and 14 days after chronic infusion of the peptide. Chronic i.c.v. infusion of Aβ(25–35) decreased SRIF-like immunoreactive content without modifying the SRIF receptor density, SRIF receptor expression, or the Giα1, Giα2, and Giα3 protein levels in the hippocampus. This treatment, however, caused a decrease in basal and forskolin-stimulated AC activity as well as in the capacity of SRIF to inhibit AC activity. Furthermore, the protein levels of the neural-specific AC type I were significantly decreased in the hippocampus of the treated rats, whereas an increase in the levels of AC V/VI was found, with no alterations in type VIII AC. A single i.c.v. dose of Aβ(25–35) exerted no effect on SRIF content or SRIF receptors but induced a slight decrease in forskolin-stimulated AC activity and its inhibition by SRIF. Because chronic Aβ(25–35) infusion impairs learning and memory whereas SRIF facilitates these functions, the alterations described here might be physiologically important given the decreased cognitive behavior previously reported in Aβ-treated rats. PB Wiley InterScience SN 1097-4547 YR 2007 FD 2007 LK http://hdl.handle.net/10017/2465 UL http://hdl.handle.net/10017/2465 LA eng DS MINDS@UW RD 25-abr-2024