TABLE 2.

Experimental findings in in vitro model of depression.

Study type	In vitro models	Depressogenic stimuli	Outcome measured	Comments	References
Mechanistic	HPCs	IL-1β	Neurogenesis	IL-1β impaired neurogenesis by activating the neurotoxic kynurenine pathway, which has been implicated in depression pathology	Zunszain et al., 2012
	HPCs	Cortisol	Neurogenesis	Cortisol impaired neurogenesis in Serum/Glucocorticoid Regulated Kinase 1-dependent manner	Anacker et al., 2013
	HPCs	IL-1β and IL-6	Neurogenesis	IL-6 impacted neurogenesis in a concentration-dependent manner	Borsini et al., 2020
	Mouse primary microglial cells BV-2 mouse microglia cells	LPS	Microglial morphological changes	Circular RNA DYM was crucial for suppressing microglial activation, which was found to be decreased in MDD patients and in vivo models of depression	Zhang et al., 2020b
	HT-22 mouse hippocampal neuronal cells	Corticosterone	Cell proliferation	microRNAs rescues corticosterone induced impaired neurogenesis by inhibiting Sgk1	Jin et al., 2016
	Co-culture of primary microglial cells and NPSCs obtained from mice	Primed microglia isolated from IFN-γ-injected mice	Neuronal proliferation	Impaired neurogenesis has been associated with depression, and microglial inflammatory activation played a crucial role	Zhang et al., 2020a
Pharmacological	Primary microglial cells Mixed glial cell culture	LPS	Antidepressant activity of amitriptyline and nortriptyline	The anti-inflammatory activity of these drugs partially explained the multifactorial pathogenesis of depression, including neuroinflammation	Obuchowicz et al., 2006
	Primary microglial cells BV-2 mouse microglia cells	LPS	Antidepressant activity of fluoxetine	The therapeutic efficacy of fluoxetine was partially due to modulation of microglial activation	Liu et al., 2011
	N9 mouse microglial cells	LPS+ATP	Antidepressant activity of melatonin	Inhibition of microglial inflammatory activation was crucial for antidepressant activity of melatonin	Arioz et al., 2019
	Primary microglial cell culture	HMGB1/TNF-α	Antidepressant activity of arctigenin	Targeting microglial inflammatory activation provided a therapeutic avenue for treating depression	Xu et al., 2020