The mechanism of “dark microglia” found, a potential reason for Alzheimer’s | Science | EUROtoday

While half of humanity was devoted to killing itself within the First World War, the folks of Madrid, wearing costumes and with trumpets, took to the streets in February 1918 to have fun carnival. “Universal pain does not pray with us,” the poet Manuel Machado wrote then. A 35-year-old scientist, Pío del Río Hortega, locked himself in these days, “fleeing from the carnival hustle and bustle,” in his laboratory, close to the Atocha practice station. There he found that, by treating mind slices with silver carbonate and ammonia, cells by no means seen earlier than within the human thought organ had been noticed beneath a microscope. He named them microglia and, due to this discovery, he was nominated thrice to obtain the Nobel Prize in Medicine. An worldwide staff of scientists reveals this Monday a microglia mechanism concerned in Alzheimer’s, a illness that impacts some 40 million folks on this planet.

It is a little-known reality, even in Spain: three of the 4 elementary sorts of mind cells had been found by Spanish scientists. Santiago Ramón y Cajal, in 1888, was the primary to display that the nervous system was organized into particular person cells: neurons. In 1895, the Hungarian anatomist Mihály Lenhossék coined the phrase astrocytes to discuss with star-shaped cells that acted as a help for neurons. And, after the bustling Madrid carnival of 1918, Pío del Río Hortega found the opposite two sorts alone: ​​microglia, that are small cells that clear the nervous system of waste, and oligodendrocytes, which act because the insulating layer of the cells. cables of the neurons.

Also on carnival dates, however in 2016, Canadian neuroscientist Marie-Ève ​​Tremblay and her colleagues found the existence of an enigmatic “dark microglia”, a extra blackish variant – within the electron microscope – that was considerable in samples from Alzheimer’s sufferers. A brand new research, led by Turkish researcher Pinar Ayata and with Tremblay herself among the many co-authors, reveals this Monday that this darkish microglia produces and releases poisonous lipids, which injury neurons. The work, printed within the specialised journal Neuronexhibits that, in mice, inhibiting this mechanism prevents neurodegeneration. Pinar Ayata’s establishment, the City University of New York (USA), has introduced this discovering as “a promising target for drug therapies that slow and possibly reverse” Alzheimer’s.

Neuroscientist Amanda Sierra compares microglia to the Roman god Janus, who had two faces and was linked to warfare and peace. The cells found by Pío del Río Hortega act as an immune agent, which protects the nervous system towards inside or exterior aggression, however they can be dangerous. “The dark microglia state was a purely morphological description that Marie-Ève ​​Tremblay had made in 2016, but no one really understood what it meant. Now, almost 10 years later, they have been able to see that they are cells that are damaged in response to the harmful environment that exists in Alzheimer’s disease and that also contribute to the pathology. They are cells that should defend the brain, but they are damaged and what they do is damage the neurons,” says Sierra, from the Achúcarro Basque Center for Neuroscience, in Leioa, in Greater Bilbao.

The Spanish researcher recollects that, only a month in the past, the staff of German neuroscientist Mikael Simons printed that the technology of amyloid beta plaques – a protein that accumulates between neurons in Alzheimer’s – begins in microglia. “What we are beginning to see now with these studies is that these microglia participate causally in the pathology, although they are not the only cause of Alzheimer’s,” says Sierra, co-author with Marie-Ève ​​Tremblay of the e-book. Microglia in well being and illness (Springer publishing home, 2014). “I believe that this new study opens a new route that has not been explored at all and has therapeutic potential,” he celebrates.

Belgian biologist Bart De Strooper, one of many world’s main consultants on Alzheimer’s, applauds the brand new research, however considers that the function of microglia within the very complicated international strategy of dementia “remains somewhat confusing.” The cells found by Pío del Río Hortega change their features when confronted with beta amyloid plaques, emphasizes De Strooper, from University College London. “What is less clear is which changes cause neurodegeneration and which are a consequence of it; That is, if microglia adapt to neurodegeneration or cause it,” warns the Belgian.

De Strooper highlights that the brand new research “provides solid evidence” that this mechanism of poisonous lipid manufacturing is altered in darkish microglia. “It is very interesting that they have shown in an animal model that manipulating this pathway has beneficial effects on the connections between neurons, but it will take time and more research to understand how important this specific mechanism is in the general neurodegeneration of Alzheimer’s,” he clarifies. From Strooper, admirer of Pío del Río Hortega. “He is our dad,” he proclaims. Del Río Hortega, born within the Valladolid city of Portillo in 1882, was a republican and fled Spain because of the Civil War attributable to the coup d’état of 1936. A decade later, he died in exile within the Argentine metropolis of Buenos Aires, with out having acquired the Nobel.