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: Catherine Geci, Jonathan How, Haydar Alturaihi, Ujendra Kumar
• Journal: Journal of neurochemistry (J Neurochem) Vol. 101 Issue 3 Pg. 664-73 (May 2007) ISSN: 0022-3042 [Print] England
• PMID: 17254009 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• Peptide Fragments
• RNA, Messenger
• Tetrazolium Salts
• Thiazoles
• amyloid beta-protein (25-35)
• Somatostatin
• thiazolyl blue

Topics

• Amyloid beta-Peptides (pharmacology)
• Animals
• Apoptosis (drug effects)
• Cells, Cultured
• Cerebral Cortex (cytology)
• Dose-Response Relationship, Drug
• Embryo, Mammalian
• Necrosis (chemically induced)
• Neurons (drug effects)
• Peptide Fragments (pharmacology)
• RNA, Messenger (biosynthesis)
• Radioimmunoassay (methods)
• Rats
• Reverse Transcriptase Polymerase Chain Reaction (methods)
• Somatostatin (genetics, metabolism)
• Tetrazolium Salts
• Thiazoles
• Time Factors