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

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.     

Incidence of Trypanosoma cruzi transmission through breastfeeding during acute experimental Chagas disease

ObjectiveTo verify the incidence of T. cruzi transmission through breastfeeding during acute experimental Chagas’ disease.MethodsFifteen female Swiss mice were mated and, after pregnancy confirmation, placed in individual cages. A few hours after birth, the females were inoculated with 0.1 mL of blood containing approximately 3 × 10⁵ trypomastigote forms of Y strain of T. cruzi and continued breastfeeding for 25 days.ResultsIn 142 offspring examined no infection through breastfeeding was observed.ConclusionsThe low number of trypomastigote forms ingested by the newborn mice combined with biological and biochemical characteristics of blood trypomastigotes may explain the lack of transmission in this experiment.