[PCL-2] Melatonin and Child Neurological Disorders
Melatonin is a pleiotropic and neuroendocrine molecule and is produced mainly by the pineal gland under the control of the suprachiasmatic nucleus. Melatonin regulates circadian rhythm, has antioxidant properties and anti-inflammatory abilities and is speculated to be one of treatment tools for neurological disorders, including autistic spectrum disorders (ASD). Melatonin secretion has a 24-hour rhythm, in which the peak is during the midnight. We have examined the urinary level of melatonin metabolite, 6-sulphotoxymelatonin (u6SM), in child neurological disorders. Patients with Cockayne syndrome (CS), being caused by abnormalities in genes of transcription coupled repair, develop growth failure and neurological disorders, including disturbed circadian rhythms of sleep-wakefulness. The levels of u6SM was severely reduced, suggesting that the disturbed melatonin metabolism may be involved in the disorder of circadian rhythms. Xeroderma pigmentosum (XP) is a genetic disorder in DNA nucleotide excision repair, and is characterized by skin disorders and neurodegeneration, especially in XP group A (XP-A). The peak of u6SM was reduced, whereas the urinary levels of 8-OHdG and HEL, markers of oxidative DNA damage and lipid peroxidation, respectively, were increased. In contrast, patients with severe motor and intellectual disabilities demonstrated an increase in both the u6SM and urinary levels of 8-OHdG and HEL, irrespective of sleep disorders and disturbed thermoregulation. We carried out a nation-wide questionnaire survey to investigate the use of melatonin in children in Japan, and clarified the necessity of optimization of melatonin circulation, leading to the commencement of clinical practice with melatonin in children with ASD.