The neuronal trafficking of the neurotransmitter dopamine and its regulation by the membrane protein Catecholamines up in Drosophila melanogaster

The neurotransmitter dopamine and its role in neurological diseases The biogenic catecholamine dopamine (DA) functions mainly as a neurohormone and neurotransmitter. It also functions as an intermediary step in the biosynthesis of norepinephrine and epinephrine, structurally similar catecholamines that serve as cell regulators and neurotransmitters in mammals. The neurotransmitter function of DA was not discovered until late in the 20 century. Prior to this, it was predominantly thought to operate only as a biosynthetic precursor. However, its abundance in the corpus striatum of mammals relative to norepinephrine and epinephrine [2] suggested that it serves as more than just a precursor. A previous study involved the injection of rabbits with reserpine, a neurotoxin that prevents DA passage into the synaptic vesicles, causing depleted brain DA levels [4]. It was shown that the resulting catatonic state could be reversed upon administration of dihydroxy-phenylalanine (DOPA), a precursor of DA. This reversal of reserpine-induced motor syndrome was due to an increase in DA levels in the central nervous system (CNS), indisputable evidence that DA functions as a neurotransmitter. In humans, dopaminergic neurons are found in the substantia nigra, the ventral tegmental area (VTA), and the hypothalamus. From this system, axons migrate throughout the brain in four major pathways: the nigrostriatal pathway, the mesocortical pathway, the mesolimbic pathway, and the tuberoinfundibular pathway. The nigrostriatal pathway involves projections from the substantia nigra to the striatum, and this pathway is closely related to motor function. The mesocortical pathway involves projections from the VTA to the frontal cortex, an area closely related to aspects of learning and memory. The mesolimbic pathway utilizes connections from the VTA to the nucleus accumbens and is implicated in short-term memory, mood maintenance, and physical/mental coordination. Lastly, the tuberoinfundibular pathway involves the hypothalamus and the pituitary gland. This pathway is associated with metabolism, digestion, and endocrine function. Not surprisingly, DA misregulation has been shown to principally alter development, movement, learning, and memory. Therefore, the loss of dopaminergic neurons from the substantia nigra has devastating consequences. A significant reduction of dopaminergic neurons in this area can cause akinesia and tremors, both trademarks of Parkinson’s disease (PD). Conversely, abnormally high amounts of DA can result in hyperkinesia, altered behavior, and delusions, similar to Schizophrenia. DA has also been implicated in drug addiction due to its role in reward-based learning. Furthermore, DA is intrinsically unstable and will readily form free radicals through oxidation, which is proposed as a significant contributor to some forms of neurodegeneration. Additionally, mutations in the synthetic pathway of DA disrupt dopaminedependent behaviors [13]. The brain requires a very delicate, precisely controlled DA environment to maintain proper function.