TY - JOUR
T1 - Rett syndrome and neuronal development
AU - Johnston, Michael V.
AU - Blue, Mary E.
AU - Naidu, Sakkubai
PY - 2005/9
Y1 - 2005/9
N2 - The clinical signs of Rett syndrome, as well as neuropathology and brain imaging, suggest that the disorder disrupts neuronal circuits. Studies using receptor autoradiography demonstrate abnormalities in the density of excitatory glutamate and inhibitory γ-aminobutyric acid (GABA) synaptic receptors in postmortem brain from young female subjects with Rett syndrome. MeCP2, the protein that is abnormal in most female individuals with Rett syndrome, is expressed predominantly in neurons and appears during development at the time of synapse formation. Studies of nasal epithelium from patients with Rett syndrome show that the maturation of olfactory receptor neurons is impeded prior to the time of synapse formation. Recent reports indicate that MeCP2 controls the expression of brain-derived neurotrophic factor and the DNA-binding homeobox protein Dlx5. Brain-derived neurotrophic factor enhances glutamate neurotransmission at excitatory synapses, whereas Dlx5 is expressed in most GABAergic neurons and stimulates the synthesis of GABA. Taken together, this information supports the hypothesis that Rett syndrome is a genetic disorder of synapse development, especially synapses that use glutamate and GABA as neurotransmitters.
AB - The clinical signs of Rett syndrome, as well as neuropathology and brain imaging, suggest that the disorder disrupts neuronal circuits. Studies using receptor autoradiography demonstrate abnormalities in the density of excitatory glutamate and inhibitory γ-aminobutyric acid (GABA) synaptic receptors in postmortem brain from young female subjects with Rett syndrome. MeCP2, the protein that is abnormal in most female individuals with Rett syndrome, is expressed predominantly in neurons and appears during development at the time of synapse formation. Studies of nasal epithelium from patients with Rett syndrome show that the maturation of olfactory receptor neurons is impeded prior to the time of synapse formation. Recent reports indicate that MeCP2 controls the expression of brain-derived neurotrophic factor and the DNA-binding homeobox protein Dlx5. Brain-derived neurotrophic factor enhances glutamate neurotransmission at excitatory synapses, whereas Dlx5 is expressed in most GABAergic neurons and stimulates the synthesis of GABA. Taken together, this information supports the hypothesis that Rett syndrome is a genetic disorder of synapse development, especially synapses that use glutamate and GABA as neurotransmitters.
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U2 - 10.1177/08830738050200091101
DO - 10.1177/08830738050200091101
M3 - Article
C2 - 16225832
AN - SCOPUS:27144523524
SN - 0883-0738
VL - 20
SP - 759
EP - 763
JO - Journal of child neurology
JF - Journal of child neurology
IS - 9
ER -