N-docosahexaenoylethanolamide is an endogenous PKA-dependent mediator promoting neuronal differentiation of neural stem cells

Tuesday, October 09, 2012 — Poster Session I
1:00 p.m. – 3:00 p.m	Natcher Conference Center, Building 45	NIAAA	BIOCHEM-5

Author

• H-Y Kim

Abstract

Docosahexaenoic acid (DHA) has been shown to promote neuronal differentiation of neural stem cells (NSCs) in vivo and in vitro. In our previous study, we found that N-docosahexaenoylethanoamide (synaptamide), an endogenous metabolite of DHA, promotes neurite growth, synaptogenesis and synaptic protein expression, leading to enhanced glutamatergic synaptic function of hippocampal neurons. In this study, we demonstrate that synaptamide also induces neuronal differentiation of NSCs via PKA/CREB signaling pathways. We found that DHA actively metabolizes to synaptamide in cultured NSCs. Synaptamide (10 nM) increased MAP2 and Tuj-1 positive cells and the levels of these neuronal marker proteins at significantly lower concentrations compared to DHA (1 microM), without affecting NSC differentiation into glia cells. Inclusion of URB597, a fatty acid amide hydrolase inhibitor, sustained the level of synaptamide and further potentiated DHA- or synaptamide-induced increase of MAP-2 and Tuj-1 positive cells, supporting that synaptamide is principally responsible for DHA-induced neuronal differentiation of NSCs. The treatment of NSCs with synaptamide increased PKA/CREB phosphorylation, and PKA inhibitors abolished the syaptamide-induced neuronal differentiation of NSCs. Furthermore, PKA knockdown by specific shRNA blocked synaptamide-induced neuronal differentiation of NSCs. From these results, we concluded that synaptamide is an endogenous neurogenic factor acting through PKA/CREB activation.

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