Tyrosine Hydroxylase

Target Background

Tyrosine hydroxylase (TH) is a vital enzyme responsible for the generation of L-DOPA from the amino acid tyrosine. L-DOPA is the direct precursor of the neurotransmitter dopamine, and dopamine can itself be processed to produce the neurotransmitters adrenalin and noradrenalin (a.k.a. epinephrin and norepinephrin respectively). Neurons which use dopamine, adrenalin or noradrenaline, called collectively chatecholamines, must express TH. TH has a very restricted distribution in the brain but is highly expressed in the cells in which it is found. As a result antibodies to TH are useful for the identification of chatecholaminergic neurons. TH positive neurons in the rat are localized into clusters of cells most of which are in the brain stem, including notably the substantia nigra and locus ceruleus (1,2). The clusters of cells are usually referred to by a classification scheme based on that proposed by Dahlstrӧm and Fuxe, which labels cells in groups A1 - A17 and C1 to C3 (2). Subpopulations of neurons are localized in the olfactory bulb, habenula and retina. TH positive cells are also found in a subset of cells in the adrenal medulla, sympathetic ganglia, sensory ganglia and enteric ganglia (2). Numerous TH positive axons can be seen coursing through the striatum and to a much lesser degree the cortex originating from the mid brain A8, A9 and A10 nuclei. TH neurons have a huge impact on brain function and behavior but are relatively infrequent- the rat brain contains about 22,000 TH positive neurons in the A8, A9 and A10 nuclei out of a total of 200 million neurons (3). Parkinson's disease is caused by the loss of TH positive dopaminergic neurons in the substantia nigra, which are also relatively low in number (4), and perturbation of TH neurons has been implicated in Alzheimer's disease and schizophrenia (5-7). There is one mammalian gene which produces one mRNA transcript and one protein in rat but four alternate mRNA transcripts produce four slightly different forms of TH proteins in humans (8). Chicken TH was made against full length recombinant human TH based on the 524 amino acid sequence in NP_954987.2, expressed in and purified from E. coli. The antibody has an extremely high titre and can be used to study TH positive cells in culture and in sectioned material. The antibody has also been used to efficiently isolate TH positive PBMCs by FACS (9).