TYROSINE-HYDROXYLASE REGULATION IN NEUROTRANSMISSION AND NEUROPLASTICITY

The modulation of neurotransmitter synthesis is a fundamental mechanis m influencing neurotransmission and neuronal plasticity during develop ment. The regulation of the tyrosine hydroxylase (TH) has been used to elucidate specific adaptative responses in neurons. Trans-synaptic im pulse activity elicits sort- and long-term changes in the activity of TH. Acute regulation involves the activation of preexisting TH molecul es via phosphorylation and possibly through alternative splicing event s in humans, whereas long-term regulation results from an increased sy nthesis of the enzyme due in part to the transcriptional stimulation o f the TH gene. The long-term increase of TH activity was addressed usi ng the drug reserpine known to modify the secretion of neurotransmitte rs and the tetradecanoyl phorbol acetate (TPA). Inductions of TH expre ssion by reserpine in vivo as well as by TPA in vitro seem to be media ted by an AP-1 complex acting on a TPA responsive element (TRE) of the rat TH promoter indicating that the TRE-TH site plays a critical role in trans-synaptic induction. Our results also demonstrate a degree of adaption by sympathetic neurons to their environment by conversion fr om adrenergic to cholinergic phenotype.