Table 1.
Alterations in the neurotrophic factor system and cytokines in animal models used in translational depression research.
| Model | Neurotrophins | References | Cytokines | References |
|---|---|---|---|---|
| Prenatal stress | BDNF/Bdnf expression ↓ (amygdala, hippocampus) | [31–34] | IL-1β mRNA ↑ (hippocampus)
IL-10 ↓ |
[40] [41] |
| Methylation of BDNF exon IV ↑ | [31–34] | |||
| m-BDNF/pro-BDNF ↓ (hippocampus) | [36] | |||
|
| ||||
| Early postnatal stress | ||||
| (i) Early maternal separation | BDNF ↑, NGF ↑, NT-3 ↑ (dorsal and ventral hippocampus) | [55, 58, 60] | IL-1β ↑, IL-6 ↑ (blood)
chemokine ligand 7 ↓, chemokine receptor 4 ↓, IL-10 ↓, IL-1β ↓, IL-5 ↓ (brain) |
[64, 65] |
| (ii) Maternal deprivation | IGF-1 and IGF-1R mRNAs ↑ (cerebellum) | [57] | ||
| BDNF, TrkB mRNAs and proteins ↑ (cerebellum) | [56] | |||
| NGF, TrkA, p75 NTR mRNAs and protein unchanged (neocortex) | [56] | |||
|
| ||||
| Social isolation | BDNF mRNA ↓ (hippocampus) | [71] | IL-6 ↓, IL-4 ↓, TNF-α ↑, IFNγ ↑ (blood) |
[73, 74] |
|
| ||||
| Learned helplessness | BDNF ↓ or no changes (frontal cortex, hippocampus) | [95–98, 101] | Data insufficient | |
| BDNF mRNA ↓ (hippocampus) | [97, 98] | |||
| NGF ↑ (hippocampus) | [100] | |||
|
| ||||
| Chronic mild stress | BDNF ↓ (hippocampus, prefrontal cortex)
BDNF mRNA ↓ (hippocampus, hypothalamus) BDNF mRNA unchanged in hippocampus and amygdala VEGF mRNA ↓ or unchanged hippocampus |
[69, 92] [92, 108, 109] [62, 103–105] [114, 115] |
IL-1β ↑, TNF-α ↑, IL-6 ↑ (blood) | [79, 81, 82, 86, 87, 89, 90, 93] |
| IFN-γ ↑, TNF-α ↑, IL-6 ↑ (prefrontal cortex) | [94] | |||
| IL-1β ↑, TNF-α ↑, IL-10 ↓, IL-4 ↑ mRNAs (cortex) | [92] | |||
| IL-1β ↑, TNF-α ↑, IL-18 ↑, IL-4 ↑ TGF-β ↓ mRNAs (hippocampus) | [88] | |||
| IL-6 mRNA ↑ (hypothalamus) | [93] | |||
| IL-6 unchanged in brain and blood | [86] | |||
|
| ||||
| Social defeat | BDNF ↓ (hippocampus) | [124, 125] | IL-6 ↑ (hippocampus)
IL-6 mRNA ↑ in brain IL-1β unchanged in brain IL-1β, TNF-α mRNAs unchanged in brain but increased after challenge |
[124–126] [127] [125] [126, 127] |
| BDNF mRNA ↓ (hippocampus) | [128, 129] | |||
| BDNF ↑ (n. accunbens) | [131] | |||
| NGF ↑ (hippocampus of subordinates)
NGF ↑ (blood) |
[129] | |||
| FGF2, FGFR1 mRNAs ↓ (hippocampus) | [136] | |||
|
| ||||
| Olfactory bulbectomy | BDNF ↓ (hippocampus) | [149] | IL-1β ↑ (blood and brain)
TNF-α ↑ (brain) |
[151] [149] |
| BDNF mRNA ↑ (hippocampus) | [152] | |||
| NGF mRNA ↓ (hippocampus) | [151] | |||
|
| ||||
| Sickness behavior | Data insufficient | IL-1β, IL-6, TNF-α mRNAs ↑ (hypothalamus) | [172, 173] | |
Note. the data presented in Table 1 were extracted from the papers cited in the review. Most researches in the field are focused on the studies of alterations in the BDNF system and three cytokines, IL-1β, IL-6, and TNF-α, which are suggested to be principally involved in neuroinflammation associated with depression.