Parkinson’s disease, dystonia, Huntington’s disease may not seem to have much in common, except for one defect, namely that some neurons lose the ability to return to the “zero” position.
These conditions are different from each other – both in origin and characteristics – but they share certain disorders: uncontrolled body movements. Recently, research seems to have finally found the cause of these involuntary, very disabling movements.
When we move, a pulse is sent to certain neurons that are stimulated to learn the movement, and when we stop, these neurons return to the initial resting position; in people affected by this pathology, the neurons lose the ability to return to rest and thus remain in motion.
The study, conducted by researchers from the Santa Lucia Foundation Irccs and the University of Perugia, coordinated by Professor Paolo Calabresi, also involved the research group of Professor Antonio Pisani from the University of Tor Vergata, University College London, and the Carlos III Institute in Madrid. The results of the research, Hyperkinetic disorders and loss of synaptic downscaling, were then published in the journal Nature Neuroscience.
The neurons of movement
The neurons involved are those of a specific region of the brain, called the striatum, involved in movement. The electrical impulses that stimulate these neurons produce two different effects: LTP (long-term potentiation) when we move, and LTD (long-term depression) when we are at rest.
This alternation of impulses allows us, when we are young, to learn to move and improve our movements over time: first just hands and arms, then walking, biking, etc.
Indeed, thanks to these stimulations, the neurons in our brain guide these movements, adapt them to the surrounding environment, correct their trajectory when necessary, and keep them under control as if they were voluntary movements.
“This mechanism, however, only works as long as our neurons retain the ability to return to the “zero” position after each LTP or to express an LTD type behavior. And it is precisely this inability to “downscale” that we have demonstrated to be common in patients affected by Parkinson’s disease, dystonia, and Huntington’s disease.”
Says Dr. Veronica Ghiglieri, researcher at the Neurophysiology Laboratory of the Santa Lucia Foundation.
The resulting hyperkinesia
What is particular about the research is that a common cause of this disorder has been found in diseases that have different origins, such as a neurodegenerative disease caused by various factors, like Parkinson’s, alongside some of purely genetic origin such as dystonia and Huntington’s disease.
Professor Paolo Calabresi explains how their studies started precisely from Parkinson’s disease in order to study the side effects of levodopa.
“The common trait to these hyperkinesias is that the mechanism involves dopaminergic receptors. However, this study demonstrates that at the origin of uncontrolled movements is a dysfunction that appears identical even in patients with diseases not caused by a lack of dopamine.”
How to intervene
The future goal of such research will therefore be precisely to find a way to give neurons the ability to return to rest again.
Dr. Barbara Picconi, a researcher at the Neurophysiology Laboratory of the Santa Lucia Foundation, also notes that: “Without this ability (to “downscale”, ed) it is as if the neurons, called to perform a new movement, carry with them the stimuli received for previous movements, creating confusion in the control message. Imagine in these conditions a background noise that translates into uncontrolled movements and prevents the correct ones.”.
There are many therapeutic avenues that can be explored in the research, a drug, or new methods of deep neurostimulation or transcranial magnetic stimulation that allow correcting the plasticity to the neurons. The researchers still emphasize that:
“It must also be considered that our knowledge of the physiological brain is still incomplete today. Every new basic knowledge is important in itself!”
