Altered development of glutamate and GABA receptors in the basal ganglia of girls with Rett syndrome.

Rett syndrome (RS), a genetic disorder found almost exclusively in females, is associated with psychomotor regression and stereotyped hand movements. To determine whether a defect in basal ganglia amino acid neurotransmission plays a role in RS, NMDA-, AMPA-, kainate (KA)-, and metabotropic (mGluR)-type glutamate receptors (GluRs) and GABA receptors were labeled autoradiographically in the caudate, putamen, and globus pallidus of postmortem brain slices from 9 RS girls and 10 age-related controls. The cases were divided into younger (8 years or younger) and older age groups to study age-related changes in receptor binding density. We found significant reductions in AMPA and NMDA receptor density in the putamen and in KA receptor density in the caudate of older RS cases compared to controls. In contrast, mGluR density in the basal ganglia of RS patients was not altered significantly. The density of GluRs in control subjects generally showed more limited changes with age than in RS cases. In contrast to ionotropic GluRs, GABA receptor density was significantly increased in the caudate of young RS patients. The effects on GluR density in the putamen, which serves a primary motor function, were consistent with the motor deficits observed in RS, while those on amino acid transmitter receptors in the caudate may account for some cognitive features. Our studies demonstrate regional, receptor-subtype, and age-specific alterations in amino acid neurotransmitter receptors in the basal ganglia of RS girls. These changes may correlate with age-related clinical stages observed in RS.