摘要Exercise training effectively relieves anxiety disorders via modulating specific brain networks.The role of post-translational modification of proteins in this process,however,has been underappreciated.Here we performed a mouse study in which chronic restraint stress-induced anxiety-like behaviors can be attenuated by 14-day persistent treadmill exercise,in association with dramatic changes of protein phosphorylation patterns in the medial prefrontal cortex(mPFC).In particular,exercise was proposed to modulate the phosphorylation of Nogo-A protein,which drives the ras homolog family member A(RhoA)/Rho-associated coiled-coil-containing protein kinases 1(ROCK1)signaling cascade.Further mechanistic studies found that liver-derived kynurenic acid(KYNA)can affect the kynurenine metabolism within the mPFC,to modulate this RhoA/ROCK1 pathway for conferring stress resilience.In sum,we proposed that circulating KYNA might mediate stress-induced anxiety-like behaviors via protein phosphorylation modification within the mPFC,and these findings shed more insights for the liver-brain communications in responding to both stress and physical exercise.