Synaptamide (docsahexanoylethanolamide; DEA) promotes development of hippocampal neurons

Wednesday, October 26, 2011 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center	NIAAA	NEURO/BEHAV/SENSYS-18

Authors

• JW Lee
• HY Kim

Abstract

Docosahexaenoic acid (22:6n-3; DHA) increases neurite growth and synaptogenesis in cultured mouse fetal hippocampal neurons. In this study, we demonstrated that synaptamide (N-docsahexanoylethanolamide; DEA), an endogenous DHA ethanolamide derivative at low nanomolar concentrations has a remarkable effect on morphological differentiation of hippocampal neurons by increasing the population of neurons with more branches and longer neurites. In the embryonic rat hippocampal H19-7 cells, synaptamide promoted neurite growth at substantially lower concentrations in comparison to DHA. The retinoid X receptor (RXR) belongs to the family of nuclear hormone receptors that functions as a ligand-activated transcription factor and is known to be involved in the nervous system development. To test the role of RXR signaling in synaptamide-induced neurite growth we performed the cell-based dual luciferase RXR reporter assay. We found that synaptamide can activate RXR-alpha at low micromolar concentrations, indicating that synaptamide is an endogenous ligand for RXR. Form these results we suggest that metabolism of DHA to synaptamide as well as its binding to RXR may be a significant biochemical mechanism for hippocampal neurite growth, synaptogenesis leading to enhanced synaptic function. The novel synaptamide-dependent mechanism offers a new molecular insight for hippocampal neurodevelopment and function.

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