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Nobels to Brain Researchers

By Sean Henahan, Access Excellence

Washington, DC (10/10/00)- Three neuroscientists will share this year's Nobel Prize for medicine for their pioneering studies of neurotransmitters, research that led the way to a better understanding of neurological diseases and the developments of treatments for Parkinson's disease and depression.

The new laureates are Arvid Carlsson, Department of Pharmacology, University of Gothenburg; Paul Greengard, Laboratory of Molecular and Cellular Science, Rockefeller University, New York; and Eric Kandel, Center for Neurobiology and Behavior, Columbia University, New York.

Each of the awardees was recognized for his specific contributions to the understanding of how nerve cells communicate. In particular, the scientists all helped elucidate one type of signal transduction known as slow synaptic transmission. The neurotransmitter dopamine plays a key role in this process. Some of the drugs that were developed thanks to the research in this area include L-Dopa, a standard treatment for Parkinson's disease, and the antidepressant fluoxetine (Prozac).

Dr. Carlsson is credited for the critical discovery that dopamine is a transmitter in the brain that plays an essential role in muscle movement. He has also mad important discoveries regarding the pathogenesis of schizophrenia. Dr. Greengard's research elaborated the mechanism of action of dopamine and other transmitters. He determined that a neurotransmitter interacts with a cell surface receptor, triggering a cascade of reactions that activate regulatory proteins. Phosphorylation and dephosphorylation of these proteins changes their shape and function, facilitating the transmission of signals through the nervous system. Dr. Kandel, for his part, made important discoveries regarding the modification of the efficiency of synapses, providing important new information on short and long-term memory.

Key Elements of the Research

Dopamine nerve pathways in the brain. Arvid Carlsson showed that there were particularly high levels of the chemical transmitter dopamine in the so called basal ganglia of the brain, which are of major importance for instance for the control of our muscle movements. In Parkinson's disease those dopamine producing nerve cells whose nerve fibers project to the basal ganglia die. This causes symptoms such as tremor, muscle rigidity and a decreased ability to move about. Click Image to Enlarge



A message from one nerve cell to another is transmitted with the help of different chemical transmitters. This occurs at specific points of contact, synapses, between the nerve cells. The chemical transmitter dopamine is formed from the precursors tyrosine and L-dopa and is stored in vesicles in the nerve endings. When a nerve impulse causes the vesicles to empty, dopamine receptors in the membrane of the receiving cell are influenced such that the message is carried further into the cell. In the treatment of Parkinson's disease, the drug L-dopa is given, and is converted to dopamine in the brain. This compensates for the patient's lack of dopamine. Click Image to Enlarge



Paul Greengard has shown how dopamine and several other chemical transmitters exert their effects in the nerve cell. When receptors in the cell membrane are influenced by a chemical transmitter, the levels of for example the messenger molecule cAMP are elevated. This activates so called protein kinases, which cause certain "key proteins" to become phosphorylated, that is phosphate molecules are added. These protein phosphorylations lead to changes of a number of proteins with different functions in the cell. When for instance proteins in ion channels in the cell membrane are influenced, the excitability of a nerve cell and its ability to send impulses along its branches changes. Click Image to Enlarge

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