Involuntary movements, caused by some neurons unable to return to rest

Parkinson's, dystonia, Huntington's disease They apparently do not have much in common except for a single defect, which is that some neurons lose the ability to return to the “zero” position.

These diseases are different from each other-both in origin and characteristics; however, they have some disorders in common: the uncontrolled movements of the body. Recently research seems, at last, to have found the cause that causes these highly disabling involuntary movements.

When we move, an impulse is sent to certain neurons that are stimulated to learn movement; when we stop, these neurons return to their initial resting position; in people with this condition, the neurons lose the ability to return to rest and remain, therefore, in motion.

The study, conducted by researchers at the Santa Lucia Irccs Foundation and of the’University of Perugia, coordinated by the Professor Paolo Calabresi, also involved the research group of the Professor Antonio Pisani, of the University of Tor Vergata, the’University College of London and the’Carlos III Institute Madrid. Research findings, Hyperkinetic disorders and loss of synaptic downscaling, were later published by the magazine Nature Neuroscience.

The neurons of movement

The neurons involved are those in a certain region of the brain, called the striped, 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, riding a bicycle, etc.

In fact, thanks to these stimulations, neurons in our brain guide such movements, adapt them to their surroundings, when necessary correct their trajectory, and keep them under control as if they were voluntary movements.

“This mechanism works, however, only as long as our neurons retain the ability to return to the “zero” position after each LTP or to be able to express LTD-like behavior. And it is precisely this inability to “downscale” that we have shown to be common in patients with Parkinson's disease, dystonia and Huntington's disease.”.

Affirms the Dr. Veronica Ghiglieri, a researcher at the Laboratory of Neurophysiology of the Santa Lucia Foundation.

The resulting hyperkinesis

The special aspect of the research is that a common cause of this disorder was found in diseases that, however, have different origins, such as precisely a neurodegenerative disease, caused by different factors, such as Parkinson's, alongside some of purely genetic origin such as dystonia and Huntington's disease.

The Professor Paolo Calabresi explains how their studies started from Parkinson's disease itself in order to study the side effects of levodopa.

“The common feature of these hyperkinesias is that the mechanism affects dopaminergic receptors. However, this study shows that at the origin of the uncontrolled movements is a dysfunction that also occurs identically in patients with diseases that are not caused by dopamine deficiency.”.

How to intervene

The future goal then of such research will be precisely to try to find a way to give neurons the ability to return to rest again.

La Dr. Barbara Picconi, a researcher at the Laboratory of Neurophysiology of the Santa Lucia Foundation also points out that: “Without this ability (to “downscale,” ed.) it is as if the neurons, called upon to make a new movement, take with them the stimuli received for previous movements, creating a confusion in the control message. Imagine under these conditions a background noise that results in uncontrolled movements and prevents correct ones.”.

There are many therapeutic avenues one can go to investigate in research, a drug, or new methods of deep neurostimulation o transcranial magnetic stimulation that would allow correct plasticity to neurons. However, the researchers are keen to emphasize that:

“However, it should also be considered that our knowledge of the physiological brain today is still incomplete. Any new basic knowledge is important in itself!”.