In Memoriam: Nobel Laureate Arvid Carlsson, a Pioneer in Parkinson’s Treatment

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Photo: Johan Wingborg/University of Gothenburg

We regret to announce the loss of Dana Alliance member Arvid Carlsson, M.D., Ph.D., who passed away last Friday at 95 years old. Carlsson laid the groundwork for the treatment of Parkinson’s disease by discovering dopamine is a neurotransmitter that plays an important role in motor function. In 2000, this research won him the Nobel Prize in Physiology or Medicine with fellow Dana Alliance members Eric R. Kandel, M.D., and Paul Greengard, Ph.D., “for their discoveries concerning signal transduction in the nervous system.”

In 2001, Dana Alliance member John H. Byrne, Ph.D., wrote a Dana Foundation Cerebrum article to commemorate the 2000 Nobel Prize in Physiology or Medicine. He detailed Carlsson’s journey to his Nobel Prize winning research on dopamine:

Growing up in Sweden in an academic family, [Carlsson] had done his doctoral work at the University of Lund on calcium metabolism, and planned to pursue this research as an independent faculty member. Fate would have it otherwise. As he related in his Nobel lecture, he was rejected for a professorship because it was deemed that work on calcium metabolism was not central to pharmacology. Discouraged, he left the field and decided to become involved in biochemical pharmacology, which he felt had a great future. His decision was a loss for the field of calcium metabolism (which turned out to have a great future, too) but a red-letter day for the emerging field of neuroscience.

Another such day came when Carlsson, in 1955, decided to spend five months in Bernard Brodie’s laboratory at the U.S. National Institutes of Health. Brodie, studying the neurotransmitter serotonin, had shown that the antipsychotic drug reserpine led to depletion of serotonin from the brain. Moreover, Brodie had worked out a technique called spectrophotofluorometry that enabled him to monitor the levels of serotonin in the brain. Equipped with this new technology, Carlsson returned to Sweden to examine whether reserpine might also affect the levels of catecholamines, a family of substances structurally related to serotonin. He was about to discover a Rosetta stone for understanding neuronal signaling…

Returning to the University of Lund, Carlsson began examining how the serotonin-like catecholamines were affected by reserpine, the anti-psychotic drug. He improved his fluorimetric technique and used it to discover that reserpine led to the depletion not only of serotonin in the brain but also of catecholamines. Moreover, injection of animals with L-DOPA (one of the substances from which norepinephrine is formed) led to a rapid reversal of the decreased functioning caused by the reserpine. This reversal turned out to be caused not by increased synthesis of norepinephrine but by an increase in the catecholamine dopamine, the immediate precursor of norepinephrine. Carlsson realized, therefore, that dopamine itself was a neurotransmitter.

What is more, this transmitter became a key to understanding and eventually treating Parkinson’s disease. When Carlsson examined the distribution of dopamine in the brain, he found that it was highly localized in bilateral structures called basal ganglia, which are important for motor function. This led him to the hypothesis that the motor deficits associated with Parkinson’s disease result from loss of dopaminergic function. Carlsson proved to be right. By 1967, L-DOPA was being used to treat Parkinson’s disease.

Carlsson’s work also had a major impact on understanding depression and schizophrenia. He showed that drugs commonly used to treat schizophrenia acted by blocking dopamine receptors. Carlsson’s work also paved the way for the development of selective serotonin reuptake inhibitors such as Prozac and Paxil, and so for today’s revolution in the treatment of depression.

Throughout his life, Carlsson remained dedicated to academia. He worked as a professor at the University of Gothenberg in Sweden until he became professor emeritus in 1989. To this day, Carlsson’s research remains an important foundation for all drugs used to treat Parkinson’s disease. For more information about Carlsson’s life and work, see his New York Times obituary.

– Ali Chunovic

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