Previous studies demonstrated that depression-like behaviors caused by stress were dependent on HMGB1/TLR4/NF-κB and TNF-α/TNFR1/NF-κB signalling pathways in CUMS-exposed mice (Su et al., 2017; Liu et al., 2019; Lu et al., 2019). Here, TLR4 is linked to major depressive disorder.