Stress Increases Hepatic Release of Lipocalin 2 Which Contributes to Anxiety-Like Behavior in Mice

Chronic stress induces anxiety disorders via both neural pathways and circulating factors. Although many studies have elucidated the neural circuits involved in stress-coping behaviors, the origin and regulatory mechanism of peripheral cytokines in behavioural regulation under stress conditions are not fully understood. Here, we identified a serum cytokine, lipocalin 2 (LCN2), that was upregulated in participants with anxiety disorders. Using a mouse model of chronic restraint stress (CRS), circulating LCN2 was found to be related to stress-induced anxiety-like behaviour via modulation of neural activity in the medial prefrontal cortex (mPFC). These results suggest that stress increases hepatic LCN2 via a neural pathway, leading to disrupted cortical functions and behaviour. Cross talk between periphery and the central nervous system may contribute to stress associated behaviours. Here the authors identified liver-derived lipocalin 2 as a peripheral factor that elicits anxiety-like behaviours via modulating medial prefrontal neural activity.