This study demonstrates that toll-like receptor 4 (TLR4) activation drives depressive-like behaviors through dysregulation of the kynurenine pathway (KP) in a murine model of moderate TBI.<h4>Methods and results</h4>Using male C57BL/6J mice subjected to controlled cortical impact, we observed depression-like phenotypes (reduced sucrose preference, prolonged immobility in forced swimming tests) specifically at 28 days post-TBI, with an incidence of 28.13%. The gene discussed is TLR4; the disease is depressive disorder.