Green tea catechins confer potent biological properties including antioxidation and free-radical scavenging. We investigated the effect of long-term oral administration of green tea catechins (Polyphenon^R E, PE: EGCG 63%; EC 11%; EGC 6%; ECG 6%) mixed with water on the spatial cognition learning ability of young rats. The learning ability of rats administered PE (0%, 0.1%, 0.5%) for 26 wk was assessed in the partially baited 8-arm radial maze. Relative to controls, those administered PE had improved reference and working memory–related learning ability. They also had lower plasma concentrations of lipid peroxides and greater plasma ferric-reducing antioxidation power than controls. Furthermore, rats administered PE had lower hippocampus reactive oxygen species concentrations than controls. We suggest that this improvement in spatial cognitive learning ability is due to the antioxidative activity of green tea catechins.

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.