Re-cycling Paradigms: Cell Cycle Regulation in Adult Hippocampal Neurogenesis and Implications for Depression

Table 1 Summary of the cell cycle and signaling alterations implicated in neurogenesis imbalances observed in animal models of depression and mediating the pro-neurogenic effects of antidepressant drugs and stimuli

Experimental model	Proliferation/neurogenesis in the hippocampal DG	Molecular changes	Reference
Cell cycle regulators
CUS exposed mice	↓	↑ p27kip1 + cells in the SGZ of the DG	[64]
Naïve mice chronically treated with fluoxetine, imipramine and desipramine	↑	↓ p21cip expression in the SGZ of the DG	[69, 70]
CMS exposed rats treated with venlafaxine, mirtazapine, and aripiprazole	(Not assessed)	↑ Cdk5 activity and translocation of p35 activator to the membrane	[120]
Signaling pathways
Naïve animals chronically treated with fluoxetine	↑	↑ Wnt3a expression	[124]
Voluntary exercise in mice (antidepressant stimulus)	↑	↑ Notch1 activity in DCX + cells (cell cycle exit promotion)	[132]

SGZ subgranular zone, DG dentate gyrus, CUS chronic unpredictable stress, CMS chronic mild stress, DCX doublecortin [64, 69, 70, 120, 124, 132]