A new study by a joint research team from the Institute for Basic Science, the Korea Institute of Science and Technology and the Asan Medical Center in South Korea may overturn existing theories on the cause of motor symptoms in Parkinson’s.
So far, the prevalent view among Parkinson’s specialists has been that the motor symptoms occur when dopaminergic neurons – the brain cells that synthesize the chemical messenger dopamine – start dying off abnormally.
Therefore, to offset motor symptoms, doctors may prescribe people with Parkinson’s disease a drug called Levodopa which helps boost the brain’s reserve of dopamine.
However, the long-term use of Levodopa can lead to serious side effects, including erratic, involuntary movements.
But what if motor symptoms do not start with the death of dopaminergic neurons? If this were the case, it could change how researchers and medical practitioners understand Parkinson’s disease and the best way of treating it.
The South Korean research, which appears in the journal Current Biology, found that symptoms of Parkinson’s appear before the premature death of dopaminergic neurons.
In their study, the investigators worked with mouse models of Parkinson’s disease and analysed brain samples from both healthy people and people with Parkinson’s.
They found that before the dopaminergic neurons die off, they stop functioning – that is, they stop correctly synthesising dopamine – and this sets off the symptoms associated with Parkinson’s disease.
Looking at the mouse models of the condition, the researchers saw that astrocytes – star shaped, non-neuronal cells – in the brain started increasing in number when neurons in their vicinity began dying off.
At this point, a key chemical messenger called GABA also starts increasing in the brain, reaching an excessive level and stopping dopaminergic neurons from producing dopamine, though not killing them.
The researchers confirmed that this process occurs not just in animal models, but also in the brains of people with Parkinson’s disease.
However, the researchers also found that there is a way to restore the function of affected dopaminergic neurons by stopping astrocytes from synthesising GABA.
Doing this, they saw, also significantly decreased the severity of motor symptoms associated with Parkinson’s disease.
Further experiments in rats revealed another way of restoring function in dopaminergic neurons. The researchers inhibited dopamine synthesis in these neurons in otherwise healthy rat brains by using optogenetic tools — technology that uses light to control the activity of living cells.
This action induced Parkinson’s-like motor symptoms in the rats. But when the researchers used optogenetic tools once more, this time to restore function in the dormant dopaminergic neurons, the Parkinson’s-like symptoms decreased in severity.
In the future, argues the research team, these findings may lead to better ways of treating Parkinson’s disease — ways that may reverse some of the damage to important brain mechanisms.