. 2022 Jun 6;19:132. doi: 10.1186/s12974-022-02492-0

Table 1.

Traditional antidepressants regulate the microglia-mediated neuroinflammation in animal models of depression

Treatment	Animal models	Behavioral test	Analyzed regions	Microglia	Pro-inflammation	Anti-inflammation
Fluoxetine [154]	CSDS	OFT, EPM, SIT	Serum	—	ELISA: TNF-α ↓, HMGB1 ↑	—
Fluoxetine [154]	CSDS	OFT, EPM, SIT	Hip	Iba-1(–)	mRNA:TNF-α, IL-1β, RAGE, TLR4 ↑ Proteins: T-HMGB1, T-p65, IκB ↑, TLR4 ↓	mRNA: Arg-1, CD206 ↑
Fluoxetine [170]	CMS	Nest-building test, Dexamethasone suppression test	Cortical	CD11 b/P2X7R⁺↓	—	—
			Amygdala	CD11 b/P2X7R⁺↓	—	—
			HIP	CD11 b/P2X7R⁺↓	—	—
Fluoxetine [105]	CWIRS	SPT, FST, TST	HIP	Proteins: CD68, Iba-1 ↓	Proteins: IL-1β, TNF-α, iNOS ↓	—
Fluoxetine [155]	LPS	SPT, FST	HIP	Iba-1/COX-2⁺↓ in DG	ELISA: IL-1β, IL-6, TNF-α Proteins: TLR4, NLRP3 ↓	—
Citalopram [101]	CMS	SPT, FST	HIP	Iba-1⁺↑; CX3CL1⁺↑, CX3CR1⁺↑ in DG	—	—
Escitalopram [16]	CMS	OFT, SPT, TST, FST, NSFT	HIP	—	Proteins: IL-6, IL-1β ↓	IL-10 (–)
Escitalopram [16]	CMS	OFT, SPT, TST, FST, NSFT	Cerebral cortex	—	Protein: TNF-α ↓	IL-10 (–)
Imipramine [107]	CSDS	SIT, SPT, TST, FST	Serum	—	ELISA: IL-1β, IL-6, TNF-α ↓	—
Imipramine [107]	CSDS	SIT, SPT, TST, FST	HIP	Iba-1⁺↓ in DG	mRNA: IL-1β, IL-6, TNF-α ↓ Proteins: p-p65/p65, cleved-Caspase-3, ac-NF-κB ↓	—
Sertraline [171]	CMS	SPT, TST, FST	PFC	Iba-1/HMGB1⁺↓	Proteins: TNF-α, IL-1β ↓	—
Sertraline [171]	CMS	SPT, TST, FST	Serum	—	ELISA: TNF-α, IL-1β, NO ↓	—
Sertraline [172]	CMS	TST, FST	Brain	Protein: Iba-1 ↓	Proteins: TNF-α, iNOS, IL-1β, p-p65-NF-κB, p65-NF-κB, p-IκB-α ↓	—
Sertraline [172]	CMS	TST, FST	Serum	—	ELISA: TNF-α, IL-1β ↓	—
Vortioxetine [17]	LPS	OFT, SPT, NORT	Dorsal HIP	mRNA: CD14, CD86 ↑	mRNA: TNF-α, IL-6, IDO1 ↑	mRNA: IL-4, TGF-β1 ↑
Vortioxetine [17]	LPS	OFT, SPT, NORT	Ventral hippocampus (vHIP)	mRNA: CD14, CD86, CD11b ↑	mRNA: IL-1β, IL-6, IDO1 ↑	mRNA: IL-4, IL-1Rα ↑
Imipramine [173]	Repeated social defeat	OFT, social avoidance test	Plasma	—	ELISA: IL-6, CORT ↓	—
Imipramine [173]	Repeated social defeat	OFT, social avoidance test	Brain	Proteins: CD45, CD11b ↓	—	—
Imipramine [156]	LH	—	Hilus	Iba-1⁺↓	—	—
Clomipramine [131]	LPS	TST, FST	HIP	Iba-1⁺↓	mRNA: IL-1β, TNF-α, IL-6 ↓	—
Agomelatine [174]	LPS	—	vHIP	mRNA: CD11b, CX3CL1, CX3CR1 ↓, CD68 ↑	—	—
Melation [70]	LPS	TST, FST	HIP	Iba-1/NLRP3⁺↓	Proteins: pro-IL-1β, IL-1β, NLRP3, caspase-1	—
SRT2104 [175]	CMS	OFT, SPT, TST, FST	HIP	Iba-1⁺, CD11b⁺ CD45^low+ (–)	mRNA: IL-6, IL-1β, iNOS ↓ CD11b⁺ MHCII⁺↓	mRNA: IL-10, TGF-β, Arg-1 ↑ CD11b⁺CD206⁺↑
Pioglitazone [169]	CMS	OFT, SPT, TST, FST	HIP	Iba-1⁺↓	mRNA: IL-1β, IL-6, TNF-α, iNOS, CCL2 ↓	mRNA: Ym1, Arg1, IL-4, IL-10, TGF-β ↑
Clemastine [176]	CMS	SPT, TST, FST	Serum	—	ELISA: IL-1β, TNF-α ↓	—
Clemastine [176]	CMS	SPT, TST, FST	HIP	Protein: Iba-1 ↓	Proteins: IL-1β, TNF-α, iNOS ↓	Protein: Arg-1 ↑
Minocycline [163]	OBX + spinal nerve ligation	OFT	PFC	—	mRNA: IL-1β, IL-6 ↑	mRNA: MRC2, IL-10 ↑
Minocycline [14]	CMS	SPT, FST, EMP	Serum	—	CORT ↓	—
Minocycline [14]	CMS	SPT, FST, EMP	HIP	mRNA: CD11b, IFN-γ/IL-4, IFN-γ/IL-10 ↓	mRNA: IFN-γ, TNF-α, IL-1β, IL-17 ↓ Protein: CD11b ↓	mRNA: TGF-β1, IL-4, IL-10, IL-13 ↑
Memantine [177]	OBX	Emotional behavior, TST, FST	HIP	Iba-1⁺↓	Proteins: p-IkBα, p-p65-NF-κB, TNF-α, IL-6 ↓	—
Iptakalim [94]	CMS	SPT, TST, FST	Serum	—	ELISA: IL-1β ↓	—
Iptakalim [94]	CMS	SPT, TST, FST	HIP	MAC-1⁺↓ in DG	mRNA: TNF-α, IL-6 Proteins: p65, IL-1β, NLRP3, caspase-1 ↓	mRNA: IL-10 ↑
Simvastatin [178]	LPS or CMS	SPT, FST, NSFT	HIP	Iba-1⁺↓	Proteins: p65-NF-κB, IL-1β, TNF-α, IL-6 ↓	—
ONO-2952 [179]	CSDS	OFT, EMP, TST, FST	NAc	—	Proteins: TNF-α, IL-6 ↓	—
			BLA	DHE/Iba1⁺↓	Proteins: IL-1β, IL-6, IL-12 ↓	—
			PFC	—	Proteins: IL-1β, IL-12 ↓	—
			vHip	—	Protein: IL-12 ↓	—
Iptakalim [180]	CRS	OFT, FST	Hypothalamus	TNF-α/CD11b⁺↓	mRNA: TNF-α, TLR4, IL-1β ↓	—
Caffeine [105]	CWIRS	SPT, FST, TST	HIP	Protein: Iba-1 ↓ CD68⁺↓	Proteins: CD68, iNOS, TNF-α, IL-1β ↓	—
Apelin-13 [181]	CWIRS	OFT, SPT, TST, FST	HIP	Iba-1⁺↑, Iba-1/iNOS⁺↑, Iba-1/Arg-1⁺↓ in CA1	Proteins: IL-1β, IL-6, iNOS ↓	Proteins: IL-1β, IL-6, Arg-1 ↑
Melatonin [101]	CMS	SPT, FST	HIP	Iba-1⁺, CX3CL1⁺, CX3CR1⁺↑ in DG	—	—
ω-3 polyunsaturated fatty acids [182]	Ovariectomized	SPT, FST, NSFT, TST	HIP	Iba-1⁺↓ in DG	mRNA: IL-1β, IL-6, TNF-α, CD68 ↓ Proteins: p-p65, IκB, iNOS ↓	mRNA: IL-4, IL-10, CD206, Arg-1 ↑ Protein: Arg-1 ↑
Fingolimod [183]	CMS	OFT, SPT, FST, WMW	HIP	mRNA: Iba-1 ↑	ELISA: IL-1β, IL-6, TNF-α ↓ mRNA: NLRP3, ACS, caspase-1, iNOS, CD16 ↓ Proteins: iNOS, CD16, NLRP3, ACS, caspase-1 ↓	ELISA: IL-10 ↑ mRNA: Arg-1, CD206 ↑ Proteins: Arg-1, CD206 ↑

↑upregulated; ↓downregulated; (–) no significant difference;—no explicit data