@misc{10481/100750, year = {2017}, url = {https://hdl.handle.net/10481/100750}, abstract = {Neural 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.}, organization = {Spanish Ministry of Economy and Competitivity (MINECO)}, organization = {Carlos III Health Institute CB/10/00238}, organization = {CEIBiotic University of Granada, Spain GREIB.PT_2010_04}, organization = {Junta de Andalucía, Spain CTS-101}, organization = {University of Antioquia in Colombia}, organization = {University of Granada in Spain}, organization = {Colciencias #1115-657-740786 (623-2014)}, organization = {Enlaza-Mundos}, organization = {AUIP mobility programs}, publisher = {Wiley}, keywords = {Alzheimer's disease}, keywords = {Parkinson's disease}, keywords = {melatonin}, keywords = {mitochondria}, keywords = {neural stem cells}, keywords = {oxidative stress}, keywords = {transplant}, title = {Melatonin enhances neural stem cell differentiation and engraftment by increasing mitochondrial function}, doi = {10.1111/jpi.12415}, author = {Mendivil-Pérez, Miguel and Soto-Mercado, Viviana and Guerra Librero Rite, Ana and Fernández Gil, Beatriz Irene and Florido Ruiz, Javier and Shen, Ying-Qiang and Tejada, Miguel Ángel and Capilla-González, Vivian and Rusanova Rusanova, Iryna and García-Verdugo, José M. and Acuña Castroviejo, Darío and López García, Luis Carlos and Vélez-Pardo Carlos and Jiménez-Del-Río, Marlene and Ferrer, José M. and Escames Rosa, Germaine}, }