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N ‐docosahexaenoylethanolamine is a potent neurogenic factor for neural stem cell differentiation
Author(s) -
Rashid Mohammad A.,
Katakura Masanori,
Kharebava Giorgi,
Kevala Karl,
Kim HeeYong
Publication year - 2013
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12255
Subject(s) - neural stem cell , creb , neurite , endocannabinoid system , gliogenesis , fatty acid amide hydrolase , cellular differentiation , microbiology and biotechnology , biology , neurogenesis , chemistry , protein kinase a , kinase , biochemistry , stem cell , transcription factor , in vitro , cannabinoid receptor , receptor , gene , agonist
Docosahexaenoic acid ( DHA ) has been shown to promote neuronal differentiation of neural stem cells ( NSC s) 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 NSC s. Differentiating NSC s were capable of synthesizing synaptamide from DHA . Treatment of NSC s with synaptamide at low nanomolar concentrations significantly increased the number of MAP 2 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 NSC s. URB 597, 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 NSC s. Similarly, NSC s obtained from FAAH KO mice exhibited greater capacity to induce neuronal differentiation in response to DHA or synaptamide compared to the wild type NSC s. 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 NSC s acting through PKA / CREB activation.