Alterations in dopaminergic function in Rett syndrome

Rett syndrome is a neurological disorder associated with cortical atrophy, stereotyped hand movements, dementia, and extrapyramidal dysfunction. Endogenous levels of dopamine and its metabolites are decreased throughout the neocortex and basal ganglia and the number of dopamine type 2 receptors are decreased in the putamen. The present study investigated changes in dopamine uptake sites and dopamine type-1 receptors in the brains of eleven Rett syndrome patients (4-30 yrs) and ten normal female controls (2.5-20 yrs). The number of dopamine type 1 receptors within the caudate nucleus were unchanged. The density of dopamine reuptake sites were unchanged in the cingulate and midfrontal gyri but decreased within the caudate nucleus and putamen. The results of the present study suggest that: 1) in the basal ganglia of Rett syndrome patients, dopamine receptive neurons are intact whereas the number and activity of dopamine terminals are decreased, and 2) in the midfrontal and cingulate cortex, dopaminergic neuronal activity may be increased in order to compensate for fewer terminals that contain less dopamine.