Oxytocin activates dual Gq and Gi pathways in cultured astrocytes, mediating both excitatory and inhibitory Ca2+ signals.

The role of glial cells, particularly astrocytes, in modulating brain function is increasingly recognized, extending beyond mere support to active involvement in synaptic transmission and plasticity. While oxytocin is well-known for its neuromodulatory effects on social behavior and stress, its direct impact on glial cell function, especially astrocytes, remains an area of active investigation. Understanding how oxytocin signals through astrocytes could reveal novel therapeutic targets for conditions involving neuroinflammation or synaptic dysfunction, where astrocytic activity plays a critical role.

Researchers investigated oxytocin receptor expression and its effects in primary cortical astrocytes derived from adult rodents. They used confocal imaging to assess the presence and localization of oxytocin receptors. The study then measured the impact of oxytocin receptor activation on intracellular Ca2+ signals and glutamate release. The effects of oxytocin at nanomolar concentrations were compared to those of the biased agonists carbetocin (facilitatory) and atosiban (inhibitory) to elucidate the underlying signaling pathways. The control arm implicitly involved baseline measurements without oxytocin or agonist application.

Oxytocin receptors are expressed in both the soma and processes of astrocytes, indicating a broad potential for astrocytic modulation. The study found that oxytocin at nanomolar concentrations elicited dual responses in astrocytes: both facilitation and inhibition of Ca2+ signals and glutamate release. This complex response was further dissected using biased agonists. > The facilitatory effects of oxytocin were mimicked by carbetocin and were dependent on the activation of a Gq pathway, while the inhibitory effects were duplicated by atosiban and relied on a Gi pathway. This demonstrates that oxytocin can engage distinct G-protein coupled receptor signaling cascades within the same cell type, leading to opposing functional outcomes. These findings in cultured astrocytes mirrored previous observations in processes from astrocytes matured in neuron-astrocyte networks.