TABLE 1.

Neuroinflammatory markers in animal models of depression.

Models	Markers of neuroinflammation	Brain regions	Impact on neurons	Comments	References
CSDS	Increased IL-1β, IL-18, IL-6, and TNF-α in brain Increased microglial activation	Hippocampus Prefrontal cortex	Not discussed	Modulation of microglial activation state could be used as a therapeutic strategy to treat depressive disorders	Gu et al., 2021
CSDS	Increased mRNA of IL-1β and CCL2 in the hippocampus Increased microglial inflammatory activation	Hippocampus	Increased ΔFosB expression	IL-1 receptor pathway played a crucial role in mediating stress-induced depressive effects	DiSabato et al., 2020
CSDS CUMS CRS	Increased IL-1β, IL-18, IL-6, and TNF-α	Hippocampus	Not discussed	Increased NLRP1-inflammasome pathway was critical for the development of depression	Song et al., 2020
CRS	Increased IL-1β and caspase-1 expression	Prefrontal cortex	Not discussed	Neuroinflammatory cascades in the frontal cortex were crucial for driving depressive behaviors	MacDowell et al., 2021
CSDS CUMS CRS	Increased IL-1β and caspase-1 expression	Hippocampus	Reduced density of presynaptic proteins Impaired synaptic plasticity Altered glutamatergic neurotransmission	Caspase-1-mediated neuroinflammatory pathway impaired glutamatergic pathway leading to depression	Li et al., 2018
CRS	Increased reactive oxygen species Increased microglial inflammatory activation Increased IL-1β, IL-18	Hippocampus	Morphological changes in hippocampal neurons including enlarged pericellular spaces and irregular arrangement	Microglial GR-NF-κB-NLRP3 signaling induced depressive-like behaviors in mice	Feng et al., 2019
CUMS	Increased IL-1β and TNF-α Increased microglial activation	Prefrontal cortex Hippocampus	Neuronal dystrophy Reduced dendritic spine density	Microglial mediated neuronal remodeling induced behavioral despair and cognitive impairments	Horchar and Wohleb, 2019
CUMS	Increased IL-1β and TNF-α Increased microglial activation	Hippocampus	Neuronal atrophy Reduced dendritic spine density	Exaggerated inflammatory response in the hippocampus following exposure to stress	Xu et al., 2021
CUMS	Increased Iba-1 reactivity in stress-responsive regions Increased immune cell density in brain	Hippocampus	Reduced hippocampal neurogenesis	Targeting microglial inflammatory activation rescued stress-induced depression	Troubat et al., 2021