The catecholaminergic system of the human spinal cord

For the initiation and control of walking in humans, various regions of the central nervous system must communicate with each other. An imperative role is played by neural circuits of the spinal cord, which can autonomously coordinate rhythmic movement patterns and orchestrate the corresponding muscle groups in the legs. Communication between the brain and the spinal cord is achieved by the release of various chemical messengers, so-called neurotransmitters, which dock at specific target locations to trigger or modulate various neural actions. Many of these neurotransmitters, which are necessary for the spinal cord circuits to produce normal walking function, including dopamine and noradrenaline, are produced in the brain or brain stem and reach the spinal cord via long descending neural pathways. Following a spinal cord injury, these connections between the movement centers in the brain and the spinal cord, and consequently the transmitting pathways of the neurotransmitters, become partially or completely interrupted. The spinal cord, which is no longer supplied with the necessary neurotransmitters, or not in sufficient quantities, can no longer fulfill its function in movement control. Among the consequences are paralysis or poor movement coordination. The human spinal cord is largely unexplored with regard to its neurotransmitters and receptors the sites at which the neurotransmitters exert their actions. It is also unknown whether the human spinal cord harbors the building blocks, so-called enzymes, to produce neurotransmitters from their precursors and to transport them into the corresponding cells. Another essential question that has not been answered to date is how a spinal cord injury alters this machinery. These questions will be investigated in the present project. For this purpose, one of the largest archives of spinal cord samples worldwide is available, which includes tissues from deceased persons with intact central nervous system as well as those who had sustained a spinal cord injury. The goal is to create an atlas of the dopaminergic and noradrenergic systems in the human spinal cord, of the presence of specific receptor types and their localization, and of the enzymatic and transportation machinery. On the one hand, this knowledge is of great basic scientific value. On the other hand, it forms the indispensable basis for the future development of new therapeutic approaches for paraplegia and for the design of innovative pharmacological therapies to augment functional improvements by movement rehabilitation. The project will be carried out in cooperation between the research groups of Dr. Karen Minassian, Center for Medical Physics and Biomedical Engineering, and Prof. Romana Höftberger, Division of Neuropathology and Neurochemistry, at the Medical University of Vienna. The teams are leading experts in the fields of movement control at the level of the human spinal cord as well as of neurobiology and immunohistochemistry.