N-Docosahexaenoylethanolamine ameliorates LPS-induced brain inflammation through suppression of immune cell activation

Authors

• Park Taeyeop
• Kim Hee-Yong

Abstract

Inflammation is a widely accepted common factor among various neuropathological processes and has been implicated as a critical mechanism responsible for the progression of neurodegeneration. Brain inflammation is characterized by glial cell activation accompanied by production of inflammation-related cytokines, chemokines and nitric oxide (NO). Synaptamide (N-docosahexaenoylethanolamine) is synthesized from docosahexaenoic acid (DHA) in the brain, potently induces neurogenic differentiation of neural stem cells (NSCs) and promotes neurite growth and synaptogenesis in developing neurons. Growing evidences also suggests that DHA-derived mrtabolites have anti-inflammatory and pro-resolving effects, however, the role of synaptamide in the brain inflammation is mostly unknown. Thus, we investigated whether synaptamide reduces LPS-induced cytokine, chemokines, and iNOS expression in the brain, and explored the possible mechanisms for the effects of synaptamide. We found that synaptamide potently inhibits LPS-induced increase of TNF-α expression in microglia cells with concomitant induction of cAMP/PKA phosphorylation. Conversely, PKA inhibitors abolished the synaptamide effect on TNF-α expression. Other inflammatory cytokines, chemokine and iNOS were also suppressed. Interestingly, we also found that synaptamide inhibits LPS-induced imflammatory cytokine production in neutrophils and macrophage cells. In vivo injection of synaptamide at 5mg/kg almost completely abolished LPS-induced cytokine production in the brain. Taken together, our findings suggest that synaptamide can reduce LPS-induced brain inflammation through the action on multiple targets including neutrophils, macrophages and microglia. Synaptamide-derived anti-inflammatory mechanisms may provide a new therapeutic target to protect the inflammation-induced brain dysfunction.

Scientific Focus Area: Molecular Biology and Biochemistry

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