β‐Amyloid increases somatostatin expression in cultured cortical neurons

In β-amyloid (Aβ)-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 Aβ25–35-induced neurotoxicity on the expression of SST in cultured cortical neurons. Cultured cortical cells were exposed to Aβ25–35 and processed to determine the cellular content and release of SST into medium by radioimmunoassay and SST mRNA by RT-PCR. Aβ25–35 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 Aβ25–35 after 24 h of treatment. However, Aβ25–35 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 Aβ25–35, whereas, in the presence of higher concentrations of Aβ25–35 for extended time periods, SST-positive neurons decrease gradually. Furthermore, Aβ25–35 induces apoptosis at lower concentrations (5 and 10 μmol/L) and necrosis at higher concentrations (20 and 40 μmol/L). Consistent with the increased accumulation of SST, these data suggest that Aβ25–35 impairs cell membrane permeability. Selective sparing of SST-positive neurons at lower concentrations of Aβ25–35 at early time points directly correlates with the pathophysiology of Alzheimer’s disease.