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Melatonin enhances neural stem cell differentiation and engraftment by increasing mitochondrial function

AutorMendivil-Perez, Miguel; Capilla-González, Vivian; García Verdugo, José M.; Escames, Germaine
Palabras claveMelatonin
Alzheimer’s disease
Parkinson’s disease
Neural stem cells
Oxidative stress
Fecha de publicación2017
EditorJohn Wiley & Sons
CitaciónJournal of Pineal Research 63(2): e12415 (2017)
ResumenNeural stem cells (NSCs) are regarded as a promising therapeutic approach to protecting and restoring damaged neurons in neurodegenerative diseases (NDs) such as Parkinson's disease and Alzheimer's disease (PD and AD, respectively). However, new research suggests that NSC differentiation is required to make this strategy effective. Several studies have demonstrated that melatonin increases mature neuronal markers, which reflects NSC differentiation into neurons. Nevertheless, the possible involvement of mitochondria in the effects of melatonin during NSC differentiation has not yet been fully established. We therefore tested the impact of melatonin on NSC proliferation and differentiation in an attempt to determine whether these actions depend on modulating mitochondrial activity. We measured proliferation and differentiation markers, mitochondrial structural and functional parameters as well as oxidative stress indicators and also evaluated cell transplant engraftment. This enabled us to show that melatonin (25 μM) induces NSC differentiation into oligodendrocytes and neurons. These effects depend on increased mitochondrial mass/DNA/complexes, mitochondrial respiration, and membrane potential as well as ATP synthesis in NSCs. It is also interesting to note that melatonin prevented oxidative stress caused by high levels of mitochondrial activity. Finally, we found that melatonin enriches NSC engraftment in the ND mouse model following transplantation. We concluded that a combined therapy involving transplantation of NSCs pretreated with pharmacological doses of melatonin could efficiently restore neuronal cell populations in PD and AD mouse models depending on mitochondrial activity promotion.
DescripciónMendivil-Perez, Miguel et al.
Identificadoresdoi: 10.1111/jpi.12415
e-issn: 1600-079X
issn: 0742-3098
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