Melatonin Promotes Dopaminergic Differentiation Of Shed Derived From ASD Patients

Autism spectrum disorder (ASD) is a neurodevelopmental disorder marked by social impairments, restrictive interests, and repetitive behaviors. Sleep disturbances, a common comorbidity, can be managed with melatonin, though its clinical efficacy remains debated. Melatonin also exhibits antioxidant and potential neuroprotective effects, but its brain mechanisms are not fully understood. Human deciduous teeth contain SHED, which can differentiate into dopaminergic neurons (DN), linked to ASD pathology. Our previous work showed impaired neurite growth and mitochondrial dysfunction in ASD-DNs. This study aims to explore melatonin’s effects on these defects. SHED from ASD patients were differentiated into dopamine neurons. Expression of dopamine markers was analyzed, and neuron and mitochondrial morphology were examined using confocal microscopy. Flow cytometry assessed ROS, mitochondrial function, and ATP levels. Statistical analysis was performed with Prism 9. SHED derived from ASD patients, after differentiation into dopamine neurons (ASD-DNs), exhibited a reduction in the number of neuronal axons and a decrease in their maximum length. The number of mitochondria in the neurons was reduced, and mitochondrial localization within the neuronal branches was impaired. Additionally, ASD-DNs showed elevated ROS levels, along with decreased mitochondrial membrane potential (MMP) and ATP content. Melatonin was able to improve these conditions. SHED from ASD patients show impaired neuronal development, including reduced axonal growth, mitochondrial dysfunction, and increased oxidative stress. Melatonin treatment appears to alleviate these issues. Further studies are needed to explore the mechanisms of melatonin in ASD neural pathology.