Neurons control the expression of connexin 30 and connexin 43 in mouse cortical astrocytes

A characteristic feature of astrocytes is their high level of intercellular communication mediated by gap junctions. The two main connexins, Cx30 and Cx43, that form these junctions in astrocytes of adult brain display different developmental and regional expression, with a delayed onset of appearance for Cx30. In primary cultures of astrocytes from newborn cerebral cortex, while Cx43 is abundantly expressed, Cx30 is not detectable. In the present report, Western blot and confocal immunofluorescence analysis performed in astrocyte/neuron cocultures demonstrate that neurons upregulate the expression of Cx43 and induce that of Cx30 in subsets of astrocytes preferentially located in close proximity to neuronal soma. In Cx43 lacking astrocytes cocultured with neurons, the induction of Cx30 allows the restoration of dye coupling within islets of Cx30-positive astrocytes, indicating that intercellular channels formed by Cx30 are functional. The upregulating effect of neurons on the expression of connexins in cortical astrocytes is independent of their electrical activity and requires tight interactions between both cell types. This effect is reversed after neuronal death induced by neurotoxic treatments. Furthermore, excitotoxic treatments triggering neuronal death in vivo lead to a downregulation of both connexins in reactive astrocytes located within the area depleted in neurons. Altogether these observations indicate that the expression of the two main astrocyte connexins is tightly regulated by neurons.