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The catecholamines dopamine, epinephrine (adrenaline), and norepinephrine (noradrenaline) are the messengers of the sympathetic nervous system. The enzyme tyrosine hydroxylase (TH) catalyzes the conversion of tyrosine to 3,4-dihydroxyphenylalanine (DOPA), the rate-limiting step in catecholamine synthesis. The relationship between TH and the protein -synuclein has been implicated in the neurotoxic pathology of Lewy body disorders including Parkinson's disease and pure autonomic failure (PAF), an idiopathic, sporadic disorder that is characterized by autonomic failure without central nervous system disease.

I assayed TH activity in frozen brain and peripheral autopsy tissues from subjects with and without PAF to test the hypothesis that the observed peripheral sympathetic deinnervation and catecholamine depletion in PAF is accompanied by a loss of TH activity. This highly sensitive assay measured the conversion of tyrosine to DOPA using alumina extraction followed by liquid chromatography with electrochemical detection. I also began to investigate immunohistochemical approaches to localizing TH in autopsy specimens from the same patients, a line of future research complementary to the activity assay. The activity assay data are still undergoing final analysis and will be presented fully with the poster, but preliminary results support my hypothesis. These results suggest a profound loss of TH activity in certain peripheral tissues in the PAF patient, including the adrenal medulla and the ganglia of the autonomic nervous system, consistent with her clinical symptoms. Further elucidation of the activity of tyrosine hydroxylase in central and peripheral tissues in PAF will promote understanding of this disorder's pathogenesis and its clinical manifestations.

Last updated November 16, 2007