Abstract
Studies on sleep parameters of Rett syndrome revealed hypoactivity of the noradrenaline
(NA) and the serotonin (5HT) neuron in early infancy while preserving the function
of the dopamine (DA) and the cholinergic neurons of the pons normally. The sleep–wake
cycle remains in its development at the level of 4 months of age. Polysomnographies
also showed a decrease of the function of the nigrostriatal (NS)-DA neuron in early
childhood and suggested the development of receptor supersensitivity in late childhood.
Neurohistochemical and neuroimaging (PET) studies revealed the hypofunction of the
NS-DA neuron with receptor supersensitivity and of involvement of the cholinergic
neurons to the cortical pathology, whereas no substantial pathological or histochemical
abnormalities were observed in the NA and the 5HT neurons in the brainstem. The decrease
of tyrosine hydroxylase without neurodegenerative changes observed in the substantia
nigra of Rett syndrome had similarity to the pathology caused by excitotoxic lesion
of the pedunculopontine nuclei (PPN) observed in an animal experiments. Clinically
the grade of disability of locomotion was shown to correlate to the grade of the disabilities
of language. These clinical manifestations were also correlated to the specific loci
of the mutation in the methyl binding domain of the MECP2 gene. In rodents the axons
of the brainstem 5HT neuron involved in the morphogenesis of the brain in the early
developmental course disappear in neonates without apoptotic or degenerative changes
in the neurons. This period corresponds to the first 1.5–2 years in humans. Thus,
in Rett syndrome, the primary lesion appears in the brainstem NA and 5HT neurons which
affects development of synaptogenesis of the cortex and also dysfunction of the PPN.
The latter causes dysfunction of the DA neuron and the cholinergic neuron in the midbrain.
The mutation of the MECP2 gene may cause early transcription of the genes which prune
the axons of the aminergic neurons for the developmental morphogenesis of the central
nervous system in early infancy.
Keywords
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© 2001 Elsevier Science B.V. Published by Elsevier Inc. All rights reserved.
