Astroglial responses against Aβ initially occur in cerebral primary cortical cultures: species differences between rat and cynomolgus monkey

Abstract In the present study, we investigated how amyloid beta (Aβ) peptides initially affect neuronal cells in primary cerebral cortical cultures from rat and cynomolgus monkey. In these cultures, complicated interactions between glial and neuronal cells occur; moreover, synaptic interactions similar to those observed in vivo also occur between neuronal cells in these cultures. In this study, we applied low concentrations of Aβ to these well-characterized primary cultures to investigate how Aβ initially affects neurons or astroglial cells. In both rat and monkey cortical cultures, treatment with low concentrations of Aβ failed to drastically change or damage of neurons. Aβ treatment, however, significantly activated astrocytes, resulting in increased apolipoprotein E (ApoE) production. Rat astrocytes were more sensitive to Aβ than monkey astrocytes, and responded to Aβ via a different mechanism. In monkey astrocyte cultures, only direct treatment with Aβ increased ApoE production. In rat astrocyte cultures, however, treatment with conditioned media from cortical cultures grown with Aβ increased ApoE production, indicating that some sort of neuron-derived soluble factor(s) was also involved in activating rat astrocytes. These species differences suggest that monkey cortical cultures would be more useful as an in vitro model system to understand the details of how Aβ accumulates in the human brain, since monkeys are phylogenetically more similar to humans.