Australian scientists' recent discoveries regarding dopamine release from nerve cells should speed the development of more effective drugs for treating Parkinson’s Disease.
People with Parkinson's Disease suffer from muscle rigidity, tremor, a slowing of physical movement and, in extreme cases, a loss of physical movement. These primary symptoms are caused by the loss of dopamine producing nerve cells in the brain.
Medicines used for treating Parkinson's either provide extra dopamine or attach to the remaining nerve cells that release dopamine and regulate its release. In the latter case, no-one understands the mechanisms involved, or how to control them.
When an electrical impulse reaches the end of a dopamine nerve cell, called a synapse, it sometimes stimulates the release of dopamine. However, the successful release of dopamine is erratic and unpredictable.
Neuroscientists at Sydney’s Garvan Institute of Medical Research have developed a mathematical model and microscopy method that reveal the mechanisms behind synaptic dopamine release, and the factors that influence the probability of release. Their findings are published in the Journal of Neuroscience.
“We know that there’s an intrinsic probability of the release of a neurotransmitter, but what’s really interesting is that this release probability is regulated" said one researcher, Dr Bryce Vissel. "A neuron can make it more likely or less likely that a neurotransmitter will be released, but it can’t guarantee release. For example, it becomes more likely that a neurotransmitter will be released in a nerve pathway that is used a lot.”
Neurotransmitters are small molecules that are released from one nerve cell to act on the next nerve cell. Some are excitatory, some inhibitory, some modulatory. Dopamine is a modulator, which acts by smoothing out the excitatory and inhibitory signals to the nerve cell. All the inputs add up, and if a nerve gets enough positive signals, it fires an impulse.
Although there are roughly 100 billion nerve cells in our brains, with up to 100,000 connections each, we’re only just beginning to understand that every connection is regulated in the most extraordinarily sophisticated way, Dr Vissel explained.
“The surprising thing is that out of all this irregularity and complexity comes predictable or reliable function. Most of us can catch a ball that is thrown to us without dropping it, for example. When you think about the millions of nerve cell events in that simple act alone, it’s remarkable. Unfortunately, in Parkinson's disease this phenomenal ability to regulate movement is lost".
The research involved developing sophisticated statistical analysis protocols and mathematical models of synapses, to help de-mystify the part of the process that takes place at the dopamine nerve cell synapse. These findings may assist us in working out how drugs currently being used to treat Parkinson’s Disease regulate dopamine release.
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