Abstract
The search for methods of cognitive impairment treatment and prevention in neurological and neurodegenerative diseases is an urgent task of modern neurobiology. It is now known that various diseases, accompanied by dementia, exhibit a pronounced neuroinflammation. Considering the significant docosahexaenoic and eicosapentaenoic polyunsaturated fatty acids’ therapeutic potential, we decided to investigate and compare anti-inflammatory activity of their N-acylethanolamine derivatives. As a result, we found that both N-docosahexaenoylethanolamine (synaptamide) and N-eicosapentaenoylethanolamine (EPEA) prevents an LPS-mediated increase in the proinflammatory cytokines TNF-α and IL-6 production in the SIM-A9 microglia culture. In an in vivo experiment, synaptamide reversed an increase in LPS-mediated hippocampal TNF-α and IL-1β, but EPEA did not. However, both compounds contributed to the microglia polarization towards the M2-phenotype. Synaptamide, rather than EPEA, inhibited the Iba-1-positive microglia staining area increase. However, both synaptamide and EPEA prevented the LPS-mediated astrogliosis. A study of BDNF immunoreactivity showed that synaptamide, but not EPEA, reversed an LPS-mediated decrease in BDNF production. Despite the more pronounced anti-inflammatory activity of synaptamide, both compounds were effective in maintaining a normal level of hippocampal long-term potentiation in neuroinflammation. The results indicate a high therapeutic potential for both compounds. However, some tests have shown higher activity of synaptamide compared to EPEA.
Highlights
Preparations were activated by LPS followed by enzyme-linked immunosorbent assay (ELISA)
We found that LPS causes an increase in IL-1β production (Figure 2a)
By studying the activity of the pro-inflammatory microglia marker CD86, we found that synaptamide, in contrast to EPEA, reduced its expression
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. The use of the FAAH inhibitor (an enzyme that breaks down fatty acids ethanolamides) increased the stimulating effect of DHA on the neurite growth and synaptogenesis processes [19] An example of such derivatives is fatty acid ethanolamides, endogenous metabolites that are synthesized in nerve cells and perform specific functions [20]. The biological activity of DHA concerning neurogenesis and synaptogenesis processes is significantly enhanced by fatty acid amide hydrolase (FAAH) inhibition, an enzyme that metabolizes fatty acid ethanolamides [19,21]. This once again confirms the hypothesis that DHA biological activity is realized mainly due to metabolites. Sci. 2021, 22, 10728 parison with other ethanolamides, in this work we decided to compare the synaptamide and EPEA anti-inflammatory activity in in vitro and in vivo studies
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