Ricerc@Sapienza

Introduction: Sleep disturbances are highly prevalent in children with neurodevelopmental disabilities. Without appropriate treatment, sleep disorders can become chronic and last for many years. However, there are no sleep medications approved by the United States Food and Drug Administration and only one has been approved by the European Medicines Agency for pediatric insomnia; thus, most medications are prescribed off-label.

Serotonin (5HT) is produced by gut enterochromaffin (EC) cells and is involved in the pathogenesis of neuromotor disorders that characterize functional and inflammatory gastrointestinal diseases. Melatonin is a synthetic product of both the vertebrate pineal gland and the EC cells of gastrointestinal tract (GIT). Both melatonin and serotonin share the same biosynthetic pathway from tryptophan, but their effects are almost antagonistic.

Absence epilepsy and depression are comorbid disorders, but the molecular link between the two disorders is unknown. Here, we examined the role of the melatoninergic system in the pathophysiology of spike and wave discharges (SWDs) and depression-like behaviour in the Wistar Albino Glaxo from Rijswijk (WAG/Rij) rat model of absence epilepsy. In WAG/Rij rats, SWD incidence was higher during the dark period of the light-dark cycle, in agreement with previous findings.

Through activation of the ERK pathway nicotine, in both normal MCF-10A and low malignant breast cancer cells (MCF7), promotes increased motility and invasiveness. Melatonin antagonizes both these effects by inhibiting almost completely ERK phosphorylation. As melatonin has no effect on not-stimulated cells, it is likely that melatonin can counteract ERK-activation only downstream of nicotine-induced activation.