In 2010, 7, 8-dihydroxyflavone (DHF) was first identified as a TrkB agonist that has potent neurotropic activities [10,11]. DHF imitates the behaviour of BDNF and activates downstream signaling pathways upon DHF-TrkB binding, which improves neurogenesis and dendrite development in adult mice after brain injury [10, 11, 13]. Compared to administration of BDNF, DHF has higher affinity for TrkB and is more permeable through BBB, making it a widely used TrkB agonist since its discovery. Lately, Wang et al.demonstrated the beneficial effects of DHF on promoting newborn neuron dendritic development in aged mice [11]. Administration of 5mg/kg DHF for 2 weeks significantly increased the average dendritic length per branch and also dramatically reduced the percentage of newborn neurons with short total dendritic length [11].Alternatively, Guilloux et al.discovered that S38093, a H3 receptor antagonist, also improved dendritic morphology in aged mice hippocampus, possibly through releasing growth factors including BDNF [14]. Administration of 3mg/kg S38093 not only increased the dendritic length but also contributed to a significant increase in the number of newborn neurons with tertiary dendrites [14]. In addition, S38093 dramatically increased cell proliferation, survival and maturation in the hippocampus, which eventually improved context discrimination performance in aged mice. Guilloux et al also observed an improvement in BDNF transcripts level in aged mice treated with S38093 [14]. Previous studies suggested that blockage of H3receptor with S38093 facilitated glutamate release [15] and glutamate signaling triggered BDNF expression in the hippocampus [16]. Therefore Guilloux et al.speculated that S38093 revitalised hippocampal neurogenesis in aged mice via releasing growth factors like BDNF. S38093 also showed similar effect on mouse module of Alzheimer’s’ disease [14].