Two studies that used animal models for periodontal disease found eleveated inflammatory signaling and reduced neurotrophic support in the brain compared to that of control animals as indicated by higher TNF-α, IL-1β, IL-6 and TLR-4, increased number of activated glial cells as well as reduced BDNF (brain-derived neurotrophic factor) levels (Martínez et al., 2021; Wang et al., 2019). Here, TLR4 is linked to periodontal disorder.