PRELIMINARY EVIDENCE FOR NEURODEGENERATIVE CHANGES IN THE SUBSTANTIA-NIGRA OF RETT-SYNDROME

Rett syndrome (RS), which affects similar to 1 in 10,000 young females , is characterized by cognitive deterioration, ataxia, apraxia, rigidi ty, and stereotyped hand movements. Neuropathological features include reduction in brain size and hypopigmentation of neurons of the substa ntia nigra pars compacta (SNpc). Neurochemical and imaging studies sup port nigrostriatal involvement. The results of our preliminary studies show abnormalities in neurons of the substantia nigra (SN), including decreased numbers of neurons, ubiquitin-stained neuronal inclusion bo dies, decreased immunostaining for transmitter markers, and evidence o f cell death using terminal deoxynucleotidyl transferase (TDT)-mediate d dUTP-biotin nick end labeling (TUNEL), which labels fragmented intra nucleosomal DNA. These preliminary data represent the first evidence f or cell death in RS.