946524-43-2Relevant articles and documents
N-docosahexaenoylethanolamine is a potent neurogenic factor for neural stem cell differentiation
Rashid, Mohammad A.,Katakura, Masanori,Kharebava, Giorgi,Kevala, Karl,Kim, Hee-Yong
, p. 869 - 884 (2013)
Docosahexaenoic acid (DHA) has been shown to promote neuronal differentiation of neural stem cells (NSCs) in vivo and in vitro. Previously, we found that N-docosahexaenoylethanolamine (synaptamide), an endogenous DHA metabolite with an endocannabinoid-like structure, promotes neurite growth, synaptogenesis, and synaptic function. In this study, we demonstrate that synaptamide potently induces neuronal differentiation of NSCs. Differentiating NSCs were capable of synthesizing synaptamide from DHA. Treatment of NSCs with synaptamide at low nanomolar concentrations significantly increased the number of MAP2 and Tuj-1-positive neurons with concomitant induction of protein kinase A (PKA)/cAMP response element binding protein (CREB) phosphorylation. Conversely, PKA inhibitors or PKA knockdown abolished the synaptamide-induced neuronal differentiation of NSCs. URB597, a fatty acid amide hydrolase (FAAH) inhibitor, elevated the level of DHA-derived synaptamide and further potentiated the DHA- or synaptamide-induced neuronal differentiation of NSCs. Similarly, NSCs obtained from FAAH KO mice exhibited greater capacity to induce neuronal differentiation in response to DHA or synaptamide compared to the wild type NSCs. Neither synaptamide nor DHA affected NSC differentiation into GFAP-positive glia cells. These results suggest that endogenously produced synaptamide is a potent mediator for neurogenic differentiation of NSCs acting through PKA/CREB activation. Neural stem cells (NSCs) produce synaptamide (N-docosahexaenoylethanolamine) from docosahexaenoic acid (DHA). Synaptamide potently induces neuronal differentiation of NSCs through PKA-CREB signaling. The neurogenic capacity of NSCs is linked to the endogenous synaptamide level which depends on synaptamide stability and DHA availability in NSCs. Dietary omega-3 fatty acid intake that influences endogenous DHA and synaptamide levels may have significant impact on neurodevelopment. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.
Quantitative method for the profiling of the endocannabinoid metabolome by LC-atmospheric pressure chemical ionization-MS
Williams, John,Wood, JodiAnne,Pandarinathan, Lakshmipathi,Karanian, David A.,Bahr, Ben A.,Vouros, Paul,Makriyannis, Alexandros
, p. 5582 - 5593 (2008/03/12)
The endocannabinoid system's biological significance continues to grow as novel endocannabinoid metabolites are discovered. Accordingly, a myopic view of the system that focuses solely on one or two endocannabinoids, such as anandamide or 2-arachidonoyl glycerol, is insufficient to describe the biological responses to perturbations of the system. Rather, the endocannabinoid metabolome as a whole must be analyzed. The work described here is based on liquid chromatography coupled with atmospheric pressure chemical ionization mass spectrometry. This method has been validated to quantify, in a single chromatographic run, the levels of 15 known or suspected metabolites of the endocannabinoid system in the rat brain and is applicable to other biological matrixes. We have obtained an endocannabinoid profile specifically for the frontal cortex of the rat brain and have determined anandamide level differences following the administration of the fatty acid amide hydrolase inhibitor AM374.
