Objectives: 

Differentiation of mouse and human embryonic stem cells (ESC) results in changes of mitochondrial structure and morphology, and pattern of cytoplasm localization. ESC have few mitochondria with poorly developed cristae and restricted oxidative capacity. As cells are being differentiating, the number of mtDNA copies increase and these differentiated cells contain numerous larger mitochondria with distinct cristae groups, dense matrices and high membrane potential. These features suggest the initiation of metabolic activity through OXPHOS. An elevation in ATP content may therefore reflect a loss of stemness and the onset of differentiation. It is well know the role of melatonin in mitochondrial homeostasis, regulation the mitochondrial redox status and mtDNA transcriptional ability. Thus, a possible role for melatonin on stem cell differentiation is suggested.

Materials: 

Here, we studied the effects of melatonin on the proliferation and differentiation of the neuronal stem cells (NSC) from the subventricular zone (SVZ) of adult mice. Proliferation was evaluated by BrdU incorporation and differentiation by fluorescence-based immunocytochemistry using antibodies against Tuj1 and GFAP. Mouse mtDNA was quantified by qRT-PCR, and oxygen consumption by high-resolution repirometry. Melatonin was quantified by HPLC

Results: 

Micromolar (1-500 mM), but not nanomolar (0.01-10 nM) melatonin concentrations inhibit NSC proliferation increasing their differentiation into Tuj1-immunoreactive neurons. Melatonin also increase mitochondrial mass accompanied by increased respiratory chain activity, ATP production, and a reduction in the mitochondrial redox status.

Conclusions: 

These results support a role of melatonin on NSC physiology towards their differentiation to neurons by a mechanism involving changes in the mitochondrial metabolism.

Supported in part by grants nordm;PR/10/006 (OTRI: Universidad de Granada)