| Summary: | 碩士 === 長庚大學 === 生物醫學研究所 === 105 === Evidence for the presence of adult neurogenesis was first discovered over 50 years ago. However, the genetic factors which influence neurogenesis remain to be extensively studied. In this study, we used a high resolution method for identifying loci associated with neurogenesis by combining genetic mapping with sequencing information. We selected a candidate gene, follistatin (Fst), for further study due to its expression in the dentate gyrus. Also, we found follistatin are mainly expressed in the dorsal hippocampus. Thus, we hypothesized follistatin may also participate in mediating learning behavior. Here we show that mice deficient in brain based Fst expression feature impaired spatial learning, hippocampal neurogenesis and dendritic spine density. Next, to avoid the influence of this gene in development, we conducted the behaviour and neurogenesis experiments in tamoxifen-induced Fst KO mice, and the results show mice without Fst influence spatial learning and neurogenesis. Meanwhile, we found follistatin inducible knockout mice exhibit normal synaptic transmission but exhibit a deficit in long-term potentiation (LTP). To better understand the importance of hippocampal Fst, we injected AAV9.CMV.Cre viral vector into the hippocampus of Fst floxed mice to eliminate Fst expression, and mice without hippocampal Fst had poor performance in water maze compared with AAV9.CMV.eGFP injected control. Here, we demonstrated hippocampal follistatain play an critial role in sptial learning, adult neurogenesis and dendritic spine density.
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