The Role of Neurogenesis in Frontotemporal Lobar Degeneration and its Therapeutic Potential

  • 林 家瑋

Student thesis: Master's Thesis

Abstract

Frontotemporal lobar degeneration is a form of dementia which has progressive leads neuronal loss in the temporal and frontal lobes The characteristics of FTLD include behavioral dysfunction and abnormality of motor function Moreover the TDP-43 transgenic mice a FTLD mouse model reveal the gliosis at 2 -months of age suggesting an increased level of inflammation Neurogenesis is the process that constitutive generation of neuronal cells from neural stem cells (NSCs) Previous studies had shown that inflammatory cytokines such as TNF-? and IL-1β would intefere the neurogenesis Recently growing evidences suggest that adult neurogenesis is dysregulated in neurodegenerative disease Besides neurogenesis is involved in formation of new memory Accordingly we intend to investigate whether melatonin can ameliorate the inflammation promote neuronal differentiation of NSC and provide neuroprotective effects in FTLD-U mouse model First we found that neurogenesis was impaired in FTLD mouse model Next we performed cytokine array to further confirm that FTLD mice exhibited higher relative expression level of inflammatory cytokines and chemokines in the brain and the level of eotaxin1 was significant increased comparing to age-match control mice Based on these observation we used melatonin which had been reported to have anti-inflammation effects to test its protective potential We gave melatonin for 4 months and found that melatonin could improve behavior deficits in FTLD mouse model Final we identified that melatonin could decrease the expression level of eotaxin1 and increase the expression of pro-neural transcription factor Mash1 in vivo Together we found that melatonin supplement can resolve the inflammation in FTLD mouse model and promote the neurogenesis and improve the cognitive function This study provide a potential neuroprotective strategy for FTLD
Date of Award2016 Jul 21
Original languageEnglish
SupervisorKuen-Jer Tsai (Supervisor)

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