TABLE 1:

PRE-CLINICAL STUDIES

Model	Target	Depressive-like behavior protocol	Response	Publication
CMS	TLR4	mFST	↑ TLR4, MD2 mRNA/protein ↑ plasma LPS & corticosterone ↑ Il-1β, COX, & PGE2 mRNA ↓ 15d-PGJ2 PPARγ agonist (anti-inflammatory)	Garate I. et al. (2011)
CMS	TLR4	FST Sucrose preference Splash test Elevated plus maze	↑ Intestinal permeability ↓ZO-1, ↑COX-2 (colon) Bacterial translocation ↑ plasma LPS ↑ MAPK p38 activation ↓ Nrf2 (anti-oxidative)	Martin- Hernandez D. et al. (2016)
R-SDS	TLR2/TLR4	Social interaction Elevated plus maze	↑ TLR2, TLR4 mRNA ↑ TLR2/TLR4 DAMPs Microglial activation ↑ CD68 ↑ IL-1α and TNF	Nie X et al. (2018)
Stress Induction	TLR2/TLR4	Inescapable tail shock	↑ IL-1β, TNF, IL-6 mRNA Hippocampus	Weber MD et al. (2013)

Abbreviations- CMS: chronic mild stress; R-SDS: repeated-social defeat stress; TLR2/4: toll-like receptor 2/4; m(FST): modified forced swim test; MD2: myeloid differentiation factor 2; mRNA: message ribonucleic acid; LPS: lipopolysaccharide; IL-1β: interleukin-1beta; COX (2): cyclooxygenase-2; PGE2: prostaglandin E2; 15d-PGJ2: 15-deoxy-Δ12,14-prostaglandin J2; PPARγ: peroxisome proliferator-activated receptors gamma; ZO-1: zonula occludens-1 (tight junction); MAPK: mitogen-activated protein kinase; Nrf2: nuclear factor erythroid 2-related factor 2; DAMPs: damage-associated molecular patterns; CD68: cluster of differentiation 68; IL-1α: interleukin-1 alpha; TNF: tumor necrosis factor; IL-6: interleukin-6