As we age, mobility can become an issue. Some people will have normal age-related trouble like arthritis or reduced fitness levels, but others are affected by neurological disorders like Parkinson's disease (PD.) This devastating disease causes tremors, muscle rigidity and an inability to control movements like walking, holding objects and accomplishing daily tasks.
A research team at the Korea Advanced Institute of Science and Technology (KAIST) has completed work that details the mechanism in the brain that causes these well-known markers of PD, and this discovery will have a significant impact on the search for treatments. At present, there is no cure for Parkinson's, and no definitive assessments that can provide a definite diagnosis. Very often, once a diagnosis is made the loss of function is permanent. An estimated 10 million people live with PD around the globe, so finding out what causes it is crucial.
The team at KAIST worked with colleagues at Nanyang Technological University in Singapore, and the work is an entirely new look at decades of previous research. Professor Daesoo Kim from the Department of Biological Sciences at KAIST and Professor George Augustine from the Lee Kong Chian School of Medicine led the research. Dr. Jeongjin Kim from the Korea Institute of Science and Technology (KIST), is the lead author of the study published in the August 30, 2017, edition of the journal Neuron.
Movements like writing, handling food utensils and drinking from a cup are controlled by the basal ganglia at the base of the brain. Signals from this area are transmitted 3 to the thalamus, which is deep in the cortex of the brain. Two types of transmissions are needed to control movements and keep them smooth. They are excitatory signals and inhibitory signals. A proper balance between these two neural transmission types is key. In PD, it's been an accepted theory that lower levels of dopamine will inhibit transmission and therefore upset this balance and cause the textbook tremors of the disease.
Using optogenetics (controlling neurons with light) the team at KAIST wanted to test this theory. A mouse model was chosen since it's so similar to humans. Professors Kim and Augustine used the technology of optogenetics to manipulate the transmissions 6 of neurons involved in movement. Their research showed that actively stimulating signals from the basal ganglia, caused the target neurons in the thalamus to become overactive. This is called "rebound excitation" and will produce stiff muscles and tremors. Conversely, using light to suppress this excitation will quell the tremors and allow muscles to unclench. Theoretically, this could be a way to improve the motor difficulties experienced by patients with Parkinson's.
Professor Kim explained,"This study overturns three decades of consensus on the provenance of Parkinsonian symptoms. The therapeutic implications of this study for the treatment of Parkinsonian symptoms are profound. It may soon become possible to remedy movement disorders without using L-DOPA, a precursor to dopamine." Co-author Augustine added, "Our findings are a breakthrough, both for understanding how the brain typically controls the movement of our body and how this control goes awry during Parkinson's disease and related dopamine- deficiency disorders."
The study was complex and long-term, taking five years to complete. The team hopes to do further research into how controlling the mechanism of neural transmission could
lead to better outcomes for patients with movement disorders related to dopamine levels and other neurotransmitters. The video below has more information, check it out.
Sources: Korea Advanced Institute of Science and Technology, Neuron, Parkinson's Disease Foundation