In the 1950s Carlsson discovered the neurotransmitter dopamine. The signal substance is concentrated in particular in brain regions, which are important for volitional movements - the basal ganglia. In animal experiments Carlsson was able to show that dopamine is the central control molecule for movement. He treated laboratory animals with the natural substance reserpine, which empties the dopamine storage in the brain. As expected, the animals could no longer perform spontaneous movements. Then Carlsson administered the substance L-dopa to the animals, which is converted into dopamine in the brain. The animals had lost all symptoms and were moving normally.
Carlsson could not yet know that he has discovered with L-dopa the most important drug for Parkinson's. But even then, the symptoms of reserpine-treated animals reminded him of the tremors and stiffness of people with Parkinson's disease. In fact, he found that Parkinson's patients have unusually low levels of dopamine in the basal ganglia. L-dopa significantly reduces the symptoms.
Carlsson also worked on the diseases schizophrenia and depression. He showed that drugs counteract schizophrenia by blocking the docking point for dopamine. Against the widespread depression he developed so-called serotonin blockers. The molecules prevent the uptake of the neurotransmitter serotonin, which is predominantly responsible for the symptoms of depression.
"When I started my work in the 1950s, biochemists looked all the nerve cells in the brain, " Greengard told the NARSAD Research Newsletter. That's what the young researcher wanted to change. At the end of the 1960s, Greengard found more and more evidence that nerve cells differ mainly in signal transmission. Finally, the researcher identified a dopamine receptor, the docking site for the neurotransmitter dopamine. The receptor sits in certain synapses, contact points between nerve cells. When a nerve impulse reaches the end of a nerve cell, the synapse, the cell releases stored dopamine. This migrates through the so-called synaptic cleft to the subsequent nerve cell and binds there to the dopamine receptors. They initiate a biochemical reaction that turns the chemical dopamine signal back into an electrical nerve impulse that travels through the cell. display
This signal conversion made Greencard the research focus. He discovered over 100 molecules in brain cells that analyze signals from other nerve cells and transmit an integrated nerve impulse. A particularly interesting example is DARPP-32. In the protein, the dopamine signaling pathway and that of the neurotransmitter glutamate cross. DARPP-32 only passes on the stronger signal. Dueling is carried out with phosphate groups attached via the dopamine pathway to DARPP-32 and clipped again via the glutamate route. Depending on the outcome of the phosphate battle, DARPP-32 acts on different molecules, including ion channels, which allow charged particles to flow into the nerve cell, triggering a nerve impulse.
If you had watched Kandel in his groundbreaking work, you would not have thought he was a memory researcher. He did not let people recite poetry. In front of the researcher were isolated nerve cells from the sea slug Aplysia. If Kandel gave the animals a light electric shock, the snails remained hyper-anxious for several minutes: at the slightest touch, they pulled their gills together. This short-term memory was examined by Kandel on the isolated nerve cells. He discovered a biochemical cascade of electric shock via the neurotransmitter serotonin, which intensified the electrical coupling between nerve cells for several minutes.
Then Kandel ventured to the long-term memory. If he missed Aplysia several electric shocks, the animals remembered it for days. The researchers quickly realized that the synthesis of proteins is necessary for long-term memory. The switch for this Kandel found only in 1990. The protein CREB1 activated by the electroshock several genes and causes the production of the corresponding proteins. If CREB1 is missing in the neurons, only a short-term memory is formed, but never a long-term memory. The injection of CREB1 fixes the damage.
But CREB1 does not just work in marine snails. When the researchers activated CREB1 in flies, the animals shone with a "photographic memory". Also, mice receiving the CREB1 activator Rolipram outperformed their "forgetful" colleagues. Kandel believes that the memory of people in 10 to 15 years can be improved medication. That's why he founded Memory Pharmaceuticals.Marcel Falk