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Registration Number

0218U000721, 0117U003304 , R & D reports

Title

Alterations of the cannabinoid/prostaglandin D2 receptor expression and pro-/anti-inflammatory cytokine profile under LPS-induced systemic inflammation: the action of N-stearoylethanolamine as a potent modulator of pro-inflammation response.

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Head

Kasatkina Ludmila Oleksandrivna,

Registration Date

12-02-2018

Organization

A.V.Palladin Institute of Biochemistry of National Academy of Sciences

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Systemic inflammation, which is associated with an increase in the release of proinflammatory cytokines by immune cells, leads to the development of a wide range of pathological processes. First of all, the activation of macrophages by various factors and generation of proinflammatory cytokines are the main inflammatory mediators that generate immune response and the development of local and systemic inflammation. Another important pro-inflammatory component of activated macrophages is their ability to produce reactive oxygen and nitrogen species. At various pathological conditions the infiltration of macrophages in the brain tissue occurs and activated microglia induces the cascade of neuronal damage. The injection of lipopolysaccharide in rats led to an increase in the production of H2O2 in macrophages, indicating the activation of inflammatory processes in the body of experimental animals. It was shown that in macrophages of animals with LPS-induced inflammation there is an increase in IL-10 production, which correlates with an impairement of secretion in cortical neurons and hippocampus. A correlation was found between changes in calcium homeostasis in neurons with the production of reactive oxygen species. Changes in these parameters significantly affect the homeostasis of the main excitatory neurotransmitter glutamate in the brain, which may cause neurotoxicity. It was demonstrated that in groups with systemic inflammation accompanied by neuroinflammation there is an increase in the generation of reactive oxygen species in macrophages and changes in the profile of production of IL-10. Based on the results of the work, abstract was submitted for oral report on RECOOP 8th TriNet meeting. It was found that neuroinflammation is accompanied by an increase in the level of extracellular glutamate in the synapse. Glutamate is the main excitatory neurotransmitter in the central nervous system (CNS) of mammals. It is involved in the processes of recognition, memory, learning, etc. The analysis of the production of reactive oxygen species, as well as the redistribution of Ca2+ ions, allows us to determine the stimulating factors for exocytosis of the neurotransmitter from brain nerve terminals. The analysis of the above parameters in the group of animals injected with NSE allows evaluating the potential neuroprotective properties of this compound. Using the FACS analysis on the basis of the laboratory of the partner country during the visit (10.11.2017-27.11.2017), the expression of prostaglandin (DP1, CRTH2) and cannabinoid (CB1, CB2) receptors in primary macrophages and acutely isolated neurons of the frontal cortex and hippocampus was evaluated. Differences in the expression of DP1 receptors in the cerebral cortex of mice with LPS-induced inflammation were identified. The expression of this type of receptors under inflammatory conditions was corrected with N-stearoylethanolamine.

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Гудзь Єгор Анатолійович

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2020-04-02