24 April 2019

Obesity discouraged mice curiosity

Maxim Abdulaev, "The Attic"

Scientists have found that diabetes and obesity thin the blood-brain barrier in mice, which leads to a decrease in learning ability, memory impairment and violations of research behavior. According to the authors of the study, this is the main cause of cognitive impairment in these diseases.

Previous studies have already shown that obesity and diabetes are somehow related to the disruption of the BBB. At the same time, it is known that in some pathologies of the nervous system, in which the BBB is also violated, the adenosine cell receptor Adora2a is to blame for this. Its chronic activation leads to the appearance of gaps between the endothelial cells that line the vessels from the inside. Endothelial cells are one of the parts of the BBB.

Scientists conducted an experiment on mice that were put on a diet rich in fats. Such a diet leads to obesity and the appearance of symptoms of diabetes – a high content of insulin and sugar in the blood. After 16 weeks on such a diet, scientists introduced dyes into the body of mice – the sodium salt of fluorescein and blue Evans. It turned out that both the salt and Evans' blue were in the brain, which should not be normal.

The authors of the study studied the blood vessels of mice in the brain. They saw that connectivity between endothelial cells weakened, pericytes (cells that support vascular growth and tone) degraded, and astrocytes, brain cells that also form BBB, changed their shape.

A separate group of mice on a fatty diet was injected with a drug that suppresses the activity of the Adora2a receptor. After 16 weeks, it turned out that their BBB was fine.

After that, the scientists created transgenic mice in which copies of the Adora2a receptor gene could be turned off with doxycycline, and conducted an experiment with them. Transgenic mice on a high-fat diet were compared with three other groups: with another group of transgenic mice on a normal diet, with a non-transgenic group that ate normally, and with a non-transgenic group that was on a high-fat diet. After 12 weeks, the receptor gene was turned off in groups of transgenic mice, and after 16 weeks, all four groups were tested in tests for recognizing a new object and finding a way to a visible platform in the water.

The first test was that the mice were released into an arena where there were two objects: one of them was already familiar to the mice because they had met him, and the other was not. Normally, in this test, mice spend more time at an unfamiliar object, satisfying their curiosity. Experimental nontransgenic obese mice reacted to such a stimulus indifferently, spending approximately the same amount of time at each of the objects. The other three groups behaved normally, paying more attention to the new object. According to scientists, this was caused by the fact that non-transgenic mice with obesity simply forgot about meeting with the "old" object.

In another test, a mouse was lowered into a pool of water, which it could leave after finding a platform in the pool and sitting on it for some time (the experimenter got it). This is also a cognitive test, for memory: mice are first taught to think that they can get out of the pool by climbing onto the platform, and then change the color of the water, raise its level and change the location of the platform and the location of the entrance for the mouse in each cycle.

Both transgenic and nontransgenic mice coped with this test equally successfully.

The third test – also for memory – was the Y-shaped maze habitation test, which also allows you to measure curiosity and memory. In it, obese mice, both transgenic and not, showed much less attention to the unexplored corners of the maze, but as soon as the receptors for Adora2a in transgenic rodents were turned off, they corrected themselves.

The researchers explain the difference in test results by the fact that the water test, passed by all the subjects on an equal basis, shows spatial thinking abilities, and in the object recognition test, as in the Y-test, the hippocampus plays the main role. From here, scientists concluded that the effects of obesity affect specifically this part of the brain.

The authors of the study believe that the results of the study can help protect the blood vessels of the brain from the effects of obesity and diabetes. In addition, doctors should take into account that medications that should not penetrate the BBB in healthy people can do this in those who suffer from overweight or diabetes.

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