Figure 1.

Autophagy as part of antidepressant action. To move from diseased (depressed) to healthy state, ultimately a change in neuronal activity is required (A). To achieve this, several ways of antidepressant actions are proposed including effects on hormonal systems, immune system, and neurogenesis, which all might be intertwined with autophagy (97); this figure focuses on synaptic neurotransmission. The by far most often described effect of antidepressants on synaptic neurotransmission operates through directly blocking neurotransmitter reuptake transporters (part of the membrane proteins, (B). These transporters may also be addressed through signaling pathways that regulate their expression and/or function (C), not part of this review). The role of autophagy in antidepressant action frequently is explained by maintaining protein homeostasis in general, and the functional integrity of membrane proteins involved in synaptic neurotransmission in particular (D). These membrane proteins comprise not only transport proteins, but also, e.g., presynaptic SNARE proteins engaged in neurotransmission. Given the similarity of membrane dynamic processes in autophagy and synaptic neurotransmission, and to reconcile the diverse findings of antidepressant effects on autophagy, we also discussed the hypothesis that antidepressants address pathways that change membrane organization, directly linking to synaptic neurotransmission (E).