Circadian modulation of neuroplasticity by melatonin: a target in the treatment of depression

Mood disorders are a spectrum of neuropsychiatric disorders characterized by changes in the emotional state. In particular, major depressive disorder is expected to have a worldwide prevalence of 20% in 2020, representing a huge socioeconomic burden. Currently used antidepressant drugs have poor efficacy with only 30% of the patients getting in remission after the first-line of treatment. Importantly, mood disorder patients present uncoupling of circadian rhythms. In this regard, melatonin (5-methoxy-N-acetyltryptamine) an indolamine synthesized by the pineal gland during the night, contributes to synchronize body rhythms with the environmental light/dark cycle. In this review, we describe evidence supporting antidepressant-like actions of melatonin related to the circadian modulation of neuroplastic changes in the hippocampus. We also present evidence on the role of melatonin receptors and their signaling pathways underlying modulatory effects in neuroplasticity. Finally, we briefly discuss the detrimental consequences of circadian disruption on neuroplasticity and mood disorders due to modern human's lifestyle. Together data suggest that melatonin's stimulation of neurogenesis and neuronal differentiation is beneficial to patients with mood disorders.