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 H3receptor 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].
In addition to small molecules, other studies are using natural compounds to restore hippocampal neurogenesis in healthy ageing. Tomato ethanolic extracts (TEE) has been previously reported as a natural neuroprotective agent that reverses neurogenesis impairments in Parkinson’s disease [17-19]. Recent work by Bae and colleagues further confirmed its cognitive-enhancing effect in healthy ageing. TEE treated aged-mice had shown reversal of memory impairment, increase in newborn neurons and synaptic plasticity. This restoration of hippocampal neurogenesis was attributed to enhancement of BDNF and reduction of corticosterone after oral TEE supplement to aged mice [19]. Corticosterone has been shown to down-regulate BDNF expression [20], suppress synaptic plasticity [21] and induce adult neurogenesis decline as well as cognitive impairment in rodents [22], which indicated that inhibition of corticosterone levels by TEE also involved in BDNF promotion and cognition restoration.
BDNF binds with TrkB and accomplishes neurogenesis improvement via activation of downstream signaling pathways, mainly involves with the phospholipase Cγ (PLCγ), phosphatidyl inositol-3 kinase (PI3K) and extracellular signal- regulated kinase (ERK)