Research in this laboratory is focused on study of the function of neurotrophic factors in the brain and their potential for use as therapeutic agents in treatment of human neurodegenerative disease. Among these neurdegenerative diseases are Alzheimers disease, Parkinson~s disease ALS and developmental disorders including Rett syndrome. Rett syndrome (RS) is a neurodegenerative disease affecting young females and is characterized by cognitive deterioration, ataxia, apraxia, rigidity, and stereotyped hand movements. Very little is known regarding the location or extent of degeneration in brains afected by RS. Neuropathological features include reductions in brain size and weight and hypopigmentation of neurons in the substantia nigra pars compacta (SNpc). Neurochemical and imaging studies support nigrostriatal involvement. We are using a recently described technique, terminal deoxynucleotidyl transferase (TDT)-mediated dUTP-biotin nick end labeling (TUNEL), to identify dying cells in brain tissue from RS cases. This technique specifically labels dying cells in situ by end-labeling fragmented nuclear DNA, a process which occurs in some forms of programmed cell death. Through these studies, we have found TUNEL- labeled neuronal nuclei scattered throughout the SNpc in RS brain tissue. No labeled nuclei are detected in control brains or if TDT is omitted. These data are the first anatomical evidence of active neuronal cell death in RS. Characterizing the mechanisms of neuron death is an important step in identifying potential neurotrophic factors which may be useful in treatment of neurodegenerative disease.
