Long Chain Ceramides Promote Anxiety-Like Behavior and Microglia Activation in Female Mice

Long-chain ceramides have been associated with anxiety-like behavior and priming of microglial activation. This suggests a possible lipid-immune interaction in emotional regulation.

A mixture of C16:0, C18:0, C22:0, C24:0, and C24:1 ceramides was systematically administered to adult male and female mice. Anxiety-like behavior was assessed using behavioral tests. Microglial phenotypes in the cortex, hippocampus, and striatum were evaluated via flow cytometry. Regression models examined the associations between behavior and immune markers. In vitro assays evaluated phagocytosis, gene expression, mitochondrial potential, and ROS production in microglia after ceramide exposure.

Female, but not male, mice showed anxiety-like behavior after ceramide treatment. CD86+ microglia increased in the cortex, while CD206+ microglia decreased across brain regions. Behavioral scores correlated with the presence of CD86+ cells in the cortex and CD206+ cells in the hippocampus. In vitro, ceramides enhanced phagocytosis and induced NLRP3 and TNF-α expression. Ceramides also reduced mitochondrial potential and increased ROS in microglia.

Ceramide administration was associated with anxiety-like behavior in female mice, along with changes in microglial activation. These effects appear to be associated with mitochondrial dysfunction and oxidative stress, suggesting a lipid-immune interaction that could contribute to anxiety vulnerability.