ASMT determines gut microbiota and increases neurobehavioral adaptability to exercise in female mice

作者：Liu, Weina^*; Huang, Zhuochun; Zhang, Ye; Zhang, Sen; Cui, Zhiming; Liu, Wenbin; Li, Lingxia; Xia, Jie; Zou, Yong; Qi, Zhengtang^*

来源：Communications Biology, 2023, 6(1): 1126.

DOI：10.1038/s42003-023-05520-8

• DEPRESSION-LIKE BEHAVIORS
• SYNAPTIC PLASTICITY
• MELATONIN
• STRESS
• RHYTHMS
• MODULATION
• C57BL/6
• CORTEX

N-acetylserotonin O-methyltransferase (ASMT) is responsible for melatonin biosynthesis. The Asmt gene is located on the X chromosome, and its genetic polymorphism is associated with depression in humans. However, the underlying mechanism remains unclear. Here, we use CRISPR/Cas9 to delete 20 bp of exon 2 of Asmt, and construct C57BL/6J mouse strain with Asmt frameshift mutation (Asmtft/ft). We show that female Asmtft/ft mice exhibit anxiety- and depression-like behaviors, accompanied by an obvious structural remodeling of gut microbiota. These behavioral abnormalities are not observed in male. Moreover, female Asmtft/ft mice show a lower neurobehavioral adaptability to exercise, while wild-type shows a "higher resilience". Cross-sectional and longitudinal analysis indicates that the structure of gut microbiota in Asmtft/ft mice is less affected by exercise. These results suggests that Asmt maintains the plasticity of gut microbiota in female, thereby enhancing the neurobehavioral adaptability to exercise. @@@ This study shows that mutations in the X chromosome gene Asmt cause anxiety and depression-like behavior in female mice. ASMT enhances the neurobehavioral responsiveness to exercise by maintaining the plasticity of the gut microbiota.