Hes5 is a downstream effector of Notch signaling, a pathway that has a central role in regulating hippocampal neurogenesis.54, 55 Stress, a major risk factor for depression, decreases hippocampal neurogenesis, whereas chronic antidepressant treatment normalizes neurogenesis.56 The increased expression of Hes5 by l-lactate (Figure 4d) in the hippocampus of animals subjected to the open-space FST suggests that stimulation of hippocampal neurogenesis may be involved in the chronic antidepressant-like effects of l-lactate. Here, HES5 is linked to depressive disorder.