To clarify the pathophysiology of brain and spinal cord impairment in Rett syndrome (RTT), we report on the current status of research on Rett syndrome and review the abnormalities reported in neurotransmitters, neuromodulators and other biological markers in patients with RTT. We have previously investigated the levels of various factors in the blood, plasma, and cerebrospinal fluid (CSF) of RTT patients, including biogenic amines, lactate, melatonin, pyruvate and other citric acid cycle intermediates, substance P, β-endorphin and other neuropeptides, and a neuromodulator of β-phenylethylamine. In addition, we have performed near-infrared spectroscopy of the cerebral cortices in patients with RTT and genetic studies of the methyl-CpG-binding protein 2 (MECP2) in these patients. Taken together, the multiple abnormalities we and other authors have revealed in the various neurotransmitters/neuromodulator systems explain the pervasive effects of Rett syndrome. We also discuss the possible role of plasma ghrelin and present the results of our mouse study of the MECP2-null mutation using ES cells. Finally, we consider the potential for future analyses using our recently developed iPS cell system and discuss the future perspectives for the treatment and management of this disease.
Copyright © 2010 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.