Sulfadiazine partially protects the rat temporal cortex from amyloid beta peptide (25-35)-induced alterations of the somatostatinergic system.
The aim of this study was to elucidate whether sulfadiazine, shown to improve cognitive capacity in the elderly, can prevent amyloid beta peptide (Abeta) (25-35)-induced impairment of the somatostatinergic system previously reported by our group in rat temporal cortex. Male Wistar rats were thus treated with sulfadiazine (160 mg/kg) or vehicle, via a gastric cannula, twice on the day prior to Abeta(25-35) treatment. On the following day and during 14 days, Abeta(25-35) was administered intracerebroventricularly (i.c.v.) via an osmotic minipump connected to a cannula implanted in the right lateral ventricle (300 pmol/day). Sulfadiazine (80 mg/kg) or vehicle was administered once again the last 2 days of the Abeta(25-35) infusion. All animals were sacrificed by decapitation 24 h after the last sulfadiazine dose. The findings obtained reveal that sulfadiazine partially prevents the decrease in somatostatin (SRIH)-like immunoreactivity content in the temporal cortex of rats infused with Abeta(25-35) during 14 days. In addition, sulfadiazine blocks the Abeta(25-35)-induced reduction in the SRIH receptor density and in SRIH receptor subtype 2 expression. Sulfadiazine treatment also restored the inhibitory effect of SRIH on basal adenylyl cyclase activity back to control values. Altogether, the results suggest that sulfadiazine might have beneficial effects in the early treatment of Alzheimer's disease.
Burgos-Ramos
E
E
Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain.
Puebla-Jiménez
L
L
Hernández-Pinto
A
A
Arilla-Ferreiro
E
E
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D010446:Peptide Fragments / Q000633:toxicity*; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D017481:Receptors, Somatostatin / Q000378:metabolism*; D013004:Somatostatin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013411:Sulfadiazine / Q000494:pharmacology*; D013702:Temporal Lobe / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*
D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D017481:Receptors, Somatostatin; C074636:amyloid beta-protein (25-35); D013411:Sulfadiazine; D013004:Somatostatin