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Published on: September 22, 2020
Enterochromaffin Cells Drive Anxiety-Like Behaviors in Sleep-Deprived Mice
Yifang Zhai1, Li Ma2, Lixia Zhuo3
1Department of Psychiatry, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China; Department of Anesthesiology and Perioperative Medicine, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China; Center for Brain Science, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Background:
Sleep deprivation (SD) is a potent trigger of anxiety and poses a substantial threat to mental health. Although accumulating evidence suggests that disrupted intestinal function contributes to abnormal behaviors associated with SD, the specific mechanisms by which gut-derived signals modulate SD-related anxiety remain poorly understood.
Methods:
Combining behavioral analysis, chemogenetic manipulation, and neuropharmacological approaches in a male mouse model of SD, we investigated the circuit mechanism from colonic enterochromaffin (EC) cells to hippocampal neurogenesis. The involvement of vagal afferent signaling was further probed by pharmacological blockade of 5-HT3 receptors.
Results:
We identified colonic EC cells as critical early responders to SD, whose dysfunction temporally precedes the emergence of anxiety phenotypes. Chemogenetic inhibition of EC cells mimicked the behavioral and neurogenic deficits observed after SD. Conversely, chemogenetic activation of EC cells during SD normalized 5-HT levels, rescued hippocampal neurogenesis, and alleviated anxiety-like behaviors. Mechanistically, 5-HT derived from EC cells activated vagal afferents via 5-HT3 receptors, thereby promoting hippocampal neurogenesis and reducing anxiety-like behaviors.
Conclusions:
Our findings reveal a key role for colonic EC cells in regulating emotional homeostasis during SD. These results provide novel insights into the mechanisms underlying SD-induced anxiety and highlight potential therapeutic targets for preventing anxiety related to sleep loss.
