cascades [11, 12]. These pathways all eventually induce activation and phosphorylation of cAMP response element-binding protein (CREB), the transcription factor mediating expression of genes essential for survival and development of neurons during hippocampal neurogenesis [12]. For example, higher levels of ERK and CREB phosphorylation has been detected in aged mice treated with TEE feeding [19], which demonstrated the important role of ERK/CREB pathway in promoting neurogenesis and cognition.
Improve neurogenesis via increasing IGF-1
Similar to BDNF, IGF-1 is a restorative factor that facilitates hippocampal neurogenesis and has been used as a promising therapeutic molecule to revitalise cognitive abilities in aged animals [5]. Researches in the past focused on using IGF-1 peptides to overcome cognitive deficits in aged brain. Administration of IGF-1 peptides via intracerebroventricular (ICV) infusion [23] or osmotic minipumps implants [24] has successfully increased hippocampal neurogenesis and ameliorated age-related cognitive decline. By contrast, current studies are now paying more attention to the application of genes.
Pardo et al. exemplified the potential of gene therapy via introducing adenovectors expressing IGF-1 into aged mice through delivery of ependymal route. This treatment distinctly raised IGF-1 levels in the cerebrospinal fluid (CSF), which was paralleled by the pronounced increase of hippocampal neurogenesis as well as improvement of spatial memory accuracy [25]. Importantly, for the first time, this study reported the positive effect of in vivo administration of IGF-1 on restoring astrocyte branching in aged rats [25], which could also contribute to memory improvement. Furthermore, specific introduction of IGF-1 gene to NSCs of dentate gyrus was sufficient to mitigate cognitive decline in aged mice [26]. These studies demonstrate that overexpression of IGF-1 in vivo has beneficial effect and could be considered as a therapeutic strategies to deal with ageing. In addition to gene therapy, administration of antiepileptic drugs, such as levetiracetam [27] and aripiprazole [28], has been found as promising drugs to rescue cognitive deficits. Previous researches reported that rufinamide (RUF), an antiepileptic drug, had therapeutic potential recovering functional and behavioral damage caused by diabetic neuropathy [29]. Chen et al. first