Astrocytic apelin mediates cortical neuronal function and prevents anxiety-like behaviors in mice

As a key adipokine that regulates vascular functions, apelin has recently been appreciated for its role in modulating brain functions, including its potential use in treating mental diseases. However, the precise mechanism has not been fully illustrated. Here, we demonstrate that the deprivation of astrocytic apelin in the medial prefrontal cortex led to anxiety-like behaviors in mice, accompanied by defects in neuronal dendritic morphology and neural activity. Conversely, the central replenishment of apelin reversed the behavioral deficits in these conditional knockdown models. Intervention using central apelin also effectively attenuated neuronal structural deficits and anxiety-like behaviors in mice under chronic restraint stress. These results broaden our understanding of the role of apelin in modulating mental functions and provide more possibilities for targeted interventions in mental diseases.