Melatonin: a multitasking indoleamine to modulate hippocampal neurogenesis

Abstract

Neurodegeneration affects a large number of cell types including neurons, astrocytes or oligodendrocytes, and neural stem cells. Neural stem cells can generate new neuronal populations through proliferation, migration, and differentiation. This neurogenic potential may be a relevant factor to fight neurodegeneration and aging. In the last years, we can find growing evidence suggesting that melatonin may be a potential modulator of adult hippocampal neurogenesis. The lack of therapeutic strategies targeting neurogenesis led researchers to explore new molecules. Numerous preclinical studies with melatonin observed how melatonin can modulate and enhance molecular and signaling pathways involved in neurogenesis. We made a special focus on the connection between these modulation mechanisms and their implication in neurodegeneration, to summarize the current knowledge and highlight the therapeutic potential of melatonin.

Keywords: adult hippocampal neurogenesis; aging; melatonin; neural stem cell; neurodegeneration; neuroprotection; signaling pathway; therapeutic strategy.

Figure 1

Neurogenic related pathways modulation after melatonin administration. The figure represents the possible neurogenic pathways that may be upregulated (blue: MEK/ERK1/2: mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2; TrK: tropomycin-receptor kinase; BDNF: brain-derived neurotrophic factor; ERK: extracellular regulated; Ca²⁺/CaMKII: calcium/calmodulin-dependent kinase II; PI3K/Akt: phosphatidyl inositide 3 kinase/protein kinase B; Bcl-2: B-cell lymphoma 2) or down regulated (green: Bax: bcl-2-like protein 4; GSK-3β: glycogen synthase kinase 3 beta; Fas; capase 9, 8, 3) in human after the administration of melatonin, data is depicted according to the preclinical evidence reviewed in the manuscript.