From left to right, researchers Miquel Vila, Iria Carballo-Carbajal and Ariadna Laguna. / Hospital Vall d’Hebron.
If you cut a human brain in half, you would see at a glance why the black substance receives this name. A century ago, the Russian Konstantin Tretiakoff was the first to associate the selective loss of pigmented neurons in this region with Parkinson’s disease.
The degeneration of these neurons, which produce dopamine, impacts the motor cortex and makes it difficult to control voluntary movements. This causes the symptoms of muscular rigidity, motor slowing and tremors of the pathology.
Now, the testimony of this colour can write a new story in the investigation of Parkinson’s.
Age is a risk factor due to accumulation
After three years, the human brain accumulates a pigment – similar to the one produced by the skin when it is sunburned – which darkens it without the cells’ recycling mechanism doing anything to eliminate it.
“Neuromelanin is a marker of the biological age of your brain,” says Miquel Vila, ICREA research professor at the Vall d’Hebron Research Institute (VHIR, for its acronym in Catalan).
The human brain is the only one that accumulates it and has a predilection for painting the dopaminergic neurons of the substantia nigra, hence its name. When it exceeds a threshold, the first Parkinson’s dysfunctions appear, whose main risk factor is age.
Despite the association between neuromelanin, substantia nigra and Parkinson’s disease, the role of the pigment in the disease has never been investigated because laboratory animals do not accumulate it in the same amounts.
Today, the team of neurodegenerative diseases led by Vila presents in the journal Nature Communications the first rat with neuromelanin in his brain and demonstrates the predilection of the pigment by the neurons of the substantia nigra and its correlation with Parkinson’s, which Tretiakoff had observed.
The pathological threshold
This rodent opens a new way to determine the pathological threshold of neuromelanin that would improve in humans the diagnosis of Parkinson’s disease, and even anticipate neuronal loss.
The results may also contribute to novel therapies that cleanse the pigment in the brain to rejuvenate it, activating a factor involved in the cell recycling mechanism, which has already worked in mice.
“It is surprising that neuromelanin has never been taken into account experimentally,” says Vila. The researcher has injected an enzyme into the black substance of the mouse that contributes to the production of the pigment.
For now, scientists do not know why the brain generates neuromelanin, but suspect that its synthesis would not be harmful in itself. What’s more, it could even be beneficial in protecting the cell from dopamine that fails to transmit the neuronal signal and stays in the cytoplasm around the nucleus.
The mouse designed by Vila’s team is the first step to better understand the role of neuromelanin in the process of neurodegeneration of Parkinson’s disease, a disease that only affects humans.
Carballo-Carbajal I, Laguna A, Romero-Gimenez J, Cuadros T, Bové T, Martinez-Vicente M, Parent A, Gonzalez-Sepulveda M, Peñuelas N, Torra A, Rodriguez-Galvan B, Ballabio A, Hasegawa T, Bortolozzi A, Gelpi E, Vila M. Brain tyrosinase overexpression implicates age-dependent neuromelanin production in Parkinson’s disease pathogenesis. Nature Communications (2019)
Author: Núria Jar Journalist specializing in science and technology.