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New strategy reduces brain damage in Alzheimer’s and related disorders in mice

Astrocytes are normal brain cells that are not vascular, but in their response form they can damage tissue, rather than protect it. Mice with tau tangles in their brains – a model of Alzheimer’s and related diseases – have fewer astrocytes (green) active in their brains when treated with a drop of the drug (left) than untreated mice (right ). Researchers at the University of Washington School of Medicine at St. Louis has found that stargazing reduces the risk of brain damage and inflammation in mice, a study that could lead to improved therapies for Alzheimer’s disease and related tauopathies. Credit: Carolyn Mann

Alzheimer’s disease is the most common and tauopathies, a series of neurodegenerative diseases that cause toxic tangles of the tau protein. A study by researchers at the University of Washington School of Medicine at St. Louis suggests that targeting astrocytes – the virus in the brain – reduces brain damage and inflammation in mice.

The discoveries, however, are available online Science Interpretation, highlight the important role of astrocytes in causing brain damage in tauopathies, and open up new avenues to better therapies for a group of damaged and difficult to treat conditions.

“Brain inflammation appears to be a contributing factor to the development of Alzheimer’s disease, and this inflammation leads to dementia.neuronal cells in the brain, including astrocytes, “said lead author Gilbert Gallardo, Ph.D., assistant professor of physiology. suggesting that stopping their work may be beneficial in reducing. brain swelling and delay the development of Alzheimer’s. “

Tau, commonly found in the nerves in the brain, helps to produce internal structures that give the nerves their shape. When tau is confused, though, it causes brain swelling, tissue damage and cognitive impairment. Tau causes tangles in people who carry mutations in the tau gene or who experience attacks on the brain such as repetitive strain injury or exposure to neurotoxic chemicals. In Alzheimer’s, tau tangles form at the end of the disease process, which apparently results in brain-related changes in the back such as the formation of plaques of the amyloid beta beta protein.

In many neurodegenerative conditions, the so-called responsive astrocytes — astrocytes activate in a way that cause damage, rather than protection, to the brain – are abundant in areas of neuronal damage. Previously worked on amyotrophic lateral sclerosis (ALS), a neurodegenerative disease but not tauopathy, Gallardo and colleagues discovered another astrocyte proteins that stimulate cells to absorb toxic substances and increase brain inflammation. Gallardo alleges that proteins, called alpha2-Na + / K + adenosine triphosphatase (alpha2-NKA), may expel astrocytes in Alzheimer’s disease and other tauopathies.

New technique reduces brain damage in Alzheimer's disease and related diseases, in mice

Mice have been modified by genetically modified strains of tau protein in their brains as a model for Alzheimer’s disease and related tauopathies. Treating such rats with digoxin (right) reduces brain atrophy compared to untreated rats (left). Researchers at the University of Washington School of Medicine at St. Louis found that targeting astrocytes — an inflammatory cell in the brain — reduces brain damage and inflammation in mice. Credit: Carolyn Mann

Gallardo, the first author of Carolyn Mann, then an artist at the Gallardo Laboratory, and author Celeste Karch, Ph.D., a professor of psychiatry alpha2-NKA. They examined brain samples from 80 people who died of Alzheimer’s disease; 82 who died from a condition called tauopathy development of pneumonia (PSP); and 76 who died as a result of events unrelated to neurodegeneration. The researchers found that alpha2-NKA is more common in people who die from Alzheimer’s disease or PSP compared to those who die for other reasons, suggesting that the protein may help damage the brain in two conditions.

To further investigate the role of alpha2-NKA, the researchers turned to mice that had been used to begin developing tau tangles by about 6 months. By 9 ½ months, such brain cells were damaged, lost and they burn, and lose the ability to carry out the daily activities of life like building a house. The researchers found that, like humans with tauopathies, mice that were genetically modified also had alpha2-NKA levels in their brains. Levels rose as the rats got older and swollen brain damage he persecuted.

Digoxin, a drug used to treat heart condition, intervenes with alpha2-NKA functions. Researchers have tested whether the treatment of rats with a dropoxin can reduce her tangles, brain damage and inflammation, and changes in behavior. The drug worked, and moreover, worked whether they gave space to rats less than 6 months old, when the animals began to develop tau tangles, or within 8 months, when the tangles were already formed and damage.

“The message home here is that suppressing climate change is stopping the spread of disease,” Mann said. “This is important because clinical trials for Alzheimer’s disease and related tauopathies are more focused on the elimination of neurotransmitters that are associated with neuronal dysfunction and death. But our research provides evidence that intended for inflammatory astrocytes and brain. kumburi can be the key to success in dealing with such situations. “

While Digoxin is approved by the Food and Drug Administration for certain cardiovascular conditions, its effects on brain it must be carefully studied before it can be evaluated as a potential treatment for Alzheimer’s disease and related tauopathies, Gallardo said.


In Huntington’s disease, stellar cells work with neurons in the brain


Learn more:
Carolyn N. Mann et al, Astrocytic α2-Na + / K + inhibitor ATPase inhibits astrocyte reactivity and reduces neurodegeneration in a mouse tauopathy model, Science Interpretation (2022). DOI: 10.1126 / scitranslmed.abm4107

hintNew strategy reduces brain damage in Alzheimer’s disease and related diseases in mice (2022, March 18) restored 18 March 2022 from https://medicalxpress.com/news/2022-03-strategy-brain -alzheimer-disorders-mice.html

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