Chemist Finds New Target For the Treatment of Neurodegenerative Consequences of High Blood Sugar
High blood sugar (hyperglycemia) can cause cognitive impairment, epilepsy and other neurodegenerative disorders. The main form of glucose storage in the body is glycogen. In the brain, it is stored mainly in nerve cells, astrocytes, which are formed from various polyunsaturated fatty acids. They “communicate” with each other, releasing signalling molecules — oxylipins. Until now, it was not known what happens to oxylipins when glucose levels increase. Chemists from the RUDN University and MSU have studied how hyperglycemia affects oxylipins and proposed a new therapeutic target for the treatment of brain disorders associated with hyperglycemia.
“Hyperglycemia is associated with several complications in the brain. igh glucose exposure causes astrocyte dysregulation, but its effects on the metabolism of oxylipins are relatively unknown and therefore, constituted the focus of our work”, said Sergey Goriainov, the Head of the Laboratory of Mass Spectrometry and High-resolution NMR Spectroscopy of RUDN’s Center for Collective Use.
To compare how the oxylipin profiles in the astrocytes change with different glucose levels, scientists took astrocytes from the brain of rats and placed them in an environment with normal (5.5 mmol) and high (25 mmol) glucose concentration. The biochemists then measured the profile of oxylipins using a high-performance liquid chromatography-mass spectrometer UPLC-MS/MS. Oxylipins were divided into two groups, depending on by which enzymes they were derived from their predecessors — polyunsaturated fatty acids. Then they statistically analyzed the data.
It turned out that with high glucose, the profile of oxylipins released by astrocytes changes. In an environment with a high concentration of glucose, there were about four times more oxylipins, which were obtained by cyclooxygenase (COX). At normal sugar levels, COX-oxylipins were about five picograms per milligram, and about 20at high levels. For comparison, the level of oxylipins, derived by another enzyme (lipoxygenase, LOX), hardly changed depending on the glucose level and remained at 1-3 picograms per milligram. Scientists have concluded that COX-oxylipins may become a new direction for the treatment of brain disorders that occur due to hyperglycemia.
“The data suppose a regulation of COX-mediated oxylipin synthesis as a potential new target in the treatment of brain impairment associated with hyperglycemia”, said Sergey Goriainov, the Head of the Laboratory of Mass Spectrometry and High-resolution NMR Spectroscopy of RUDN’s Center for Collective Use.
The results are published in Metabolites.
Matilda Pavlovna Mityaeva was born in 1925. In November 1942, she volunteered for frontline duty. She participated in the Great Patriotic War from November 1942 to June 1945 as part of the 53rd Infantry Division of the 475th Infantry Regiment. She was wounded twice.
The team led by Sergey Zyryanov, Head of the Department of General and Clinical Pharmacology, became the winner of the All-Russian competition of scientific projects "Technologies for Human Health".
RUDN University constantly adapts to the changes of the modern world and responds to challenges flexibly. This allows us to keep the standard of a world-class research university. The sphere of science is no exception. Peter Dokukin, Head of the Research Division, presented the updated R&D Programme at the meeting of the RUDN University Academic Council.
Matilda Pavlovna Mityaeva was born in 1925. In November 1942, she volunteered for frontline duty. She participated in the Great Patriotic War from November 1942 to June 1945 as part of the 53rd Infantry Division of the 475th Infantry Regiment. She was wounded twice.
The team led by Sergey Zyryanov, Head of the Department of General and Clinical Pharmacology, became the winner of the All-Russian competition of scientific projects "Technologies for Human Health".
RUDN University constantly adapts to the changes of the modern world and responds to challenges flexibly. This allows us to keep the standard of a world-class research university. The sphere of science is no exception. Peter Dokukin, Head of the Research Division, presented the updated R&D Programme at the meeting of the RUDN University Academic Council.