Synaptamide, an endogenous structural analogue of anandamide, is a GPCR-dependent novel mediator for neuritogenesis and synaptogenesis

Thursday, October 11, 2012 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center, Building 45	NIAAA	NEURO/BEHAV/SENSYS-17

Authors

• J.W. Lee
• G. Kharebava
• H.Y. Kim

Abstract

Docosahexaenoic acid (DHA), polyunsaturated fatty acid is highly enriched in the brain, increases neurite growth and synaptogenesis in mouse fetal neurons. We found that synaptamide (N-docsahexanoylethanolamide), an endogenous metabolite of DHA, is a potent mediator for these actions. However, signaling mechanisms for the synaptamide effects are not well understood. The heterotrimeric G protein-coupled receptors (GPCRs) are important signaling molecules for many aspects of cellular function. Stimulation of certain GPCRs leads to the rapid synthesis of cAMP through the Galpha-s subunit, which activates adenyl cyclase. It has been also reported that cAMP signals modulate competitive neurite outgrowh. To investigate whether GPCR-dependent cAMP production is a mechanism for the synaptamide-induced neuritogenesis and synaptogenesis, we examined the effects of synaptamide on the Galpha-s translocation and cAMP accumulation. We found that GFP-Galpha-s which was initially expressed at the plasma membrane translocated to the cytosol in response to the synaptamide treatment, indicating an involvement of Galpha-s activation. Moreover, synaptamide induced cAMP accumulation, transcriptional activity of CRE and CREB phosphorylation at low nM concentrations. These data suggest that synaptamide-induced neurite outgrowth and synaptogenesis may be mediated by Galpha-s-dependent cAMP signaling pathway. The novel synaptamide-dependent GPCR signaling mechanism offers a new molecular insight for neurodevelopment and function.

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