Exploring age-dependent regulation of tyrosine hydroxylase in mice lacking the dopamine transporter.

Dopamine (DA) plays a critical role in cognition and reward. Therefore, dysregulation of DA neurotransmission has been implicated in neurological diseases such as Parkinson’s disease, and psychiatric disorders such as attention-deficit hyperactive disorder. Tyrosine hydroxylase (TH) is the rate-limiting enzyme in DA synthesis and its regulation has been found to be altered in transgenic mice lacking the dopamine transporter (DAT). DAT plays a critical role in the re-uptake of DA release in the synaptic cleft, thus determining the intensity and duration of DA neurotransmission. In this study, we further explored age-dependent regulation of TH in DAT knockout (KO) mice. The DAT mice exhibited a state of hyperactivity in our 10-minute locomotor activity test, a behavioral characteristic consistent in previous studies of such mice. It was found in our research that there were no significant differences in TH and pTH levels between WT and DAT KO mice up to 3 week-old. However, a dramatic and gradual decrease of both TH and pTH levels were observed from 4 week-old to 16 week-old mice. Thus, our findings provide further evidence that DAT not only plays a role in controlling the duration of DA neurotransmission, but also in the regulation of presynaptic TH homeostasis.Bachelor of Science in Biological Science