Protective Role of Eicosapentaenoic and Docosahexaenoic and Their <i>N</i>-Ethanolamide Derivatives in Olfactory Glial Cells Affected by Lipopolysaccharide-Induced Neuroinflammation

Abstract

Neuroinflammation is a symptom of different neurodegenerative diseases, and growing interest is directed towards active drug development for the reduction of its negative effects. The anti-inflammatory activity of polyunsaturated fatty acids, eicosapentaenoic (EPA), docosahexaenoic (DHA), and their amide derivatives was largely investigated on some neural cells. Herein, we aimed to elucidate the protective role of both EPA and DHA and the corresponding N-ethanolamides EPA-EA and DHA-EA on neonatal mouse Olfactory Ensheathing Cells (OECs) after exposition to lipopolysaccharide (LPS)-induced neuroinflammation. To verify their anti-inflammatory effect and cell morphological features on OECs, the expression of IL-10 cytokine, and cytoskeletal proteins (vimentin and GFAP) was evaluated by immunocytochemical procedures. In addition, MTT assays, TUNEL, and mitochondrial health tests were carried out to assess their protective effects on OEC viability. Our results highlight a reduction in GFAP and vimentin expression in OECs exposed to LPS and treated with EPA or DHA or EPA-EA or DHA-EA in comparison with OECs exposed to LPS alone. We observed a protective role of EPA and DHA on cell morphology, while the amides EPA-EA and DHA-EA mainly exerted a superior anti-inflammatory effect compared to free acids.

Keywords

• polyunsaturated fatty acids
• <i>N</i>-eicosapentaenoyl ethanolamide
• <i>N</i>-docosahexaenoyl ethanolamide
• olfactory ensheathing cells
• neuroinflammation
• neuroprotection