title: Beta-amyloid increases somatostatin expression in cultured cortical neurons.
abstract: In beta-amyloid (Abeta)-induced neurotoxicity, activation of the NMDA receptor, increased Ca2+ and oxidative stress are intimately associated with neuronal cell death as normally seen in NMDA-induced neurotoxicity. We have recently shown selective sparing of somatostatin (SST)-positive neurons and increased SST expression in NMDA agonist-induced neurotoxicity. Accordingly, the present study was undertaken to determine the effect of Abeta25-35-induced neurotoxicity on the expression of SST in cultured cortical neurons. Cultured cortical cells were exposed to Abeta25-35 and processed to determine the cellular content and release of SST into medium by radioimmunoassay and SST mRNA by RT-PCR. Abeta25-35 induces neuronal cell death in a concentration- and time-dependent fashion, increases SST mRNA synthesis and induces an augmentation in the cellular content of SST. No significant changes were seen on SST release at any concentration of Abeta25-35 after 24 h of treatment. However, Abeta25-35 induces a significant increase of SST release into medium only after 12 h in comparison with other time points. Most significantly, SST-positive neurons are selectively spared in the presence of a lower concentration of Abeta25-35, whereas, in the presence of higher concentrations of Abeta25-35 for extended time periods, SST-positive neurons decrease gradually. Furthermore, Abeta25-35 induces apoptosis at lower concentrations (5 and 10 micromol/L) and necrosis at higher concentrations (20 and 40 micromol/L). Consistent with the increased accumulation of SST, these data suggest that Abeta25-35 impairs cell membrane permeability. Selective sparing of SST-positive neurons at lower concentrations of Abeta25-35 at early time points directly correlates with the pathophysiology of Alzheimer's disease.
authors.affiliation: Department of Medicine, Royal Victoria Hospital, Montreal, Quebec, and Faculty of Pharmaceutical Science, Department of Pharmacology and Toxicology, University of British Columbia, Vancouver, Canada.
authors.forename: Catherine
authors.initials: C
authors.lastname: Geci
authors.forename: Jonathan
authors.initials: J
authors.lastname: How
authors.forename: Haydar
authors.initials: H
authors.lastname: Alturaihi
authors.forename: Ujendra
authors.initials: U
authors.lastname: Kumar
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D009336:Necrosis / Q000139:chemically induced; D009474:Neurons / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011863:Radioimmunoassay / Q000379:methods; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013004:Somatostatin / Q000235:genetics / Q000378:metabolism*; D013778:Tetrazolium Salts; D013844:Thiazoles; D013997:Time Factors
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D012333:RNA, Messenger; D013778:Tetrazolium Salts; D013844:Thiazoles; C074636:amyloid beta-protein (25-35); D013004:Somatostatin; C022616:thiazolyl blue