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Title: The expression and roles of Nde 1 and Ndel 1 in the adult mammalian central nervous system
Author: Pei, Zhe
ISNI:       0000 0004 2726 1534
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2012
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Mental or neurological illnesses affect one in four people worldwide. These diseases are economic burdens on the country. They also reduce the life quality of patients and their families. Whilst genetic linkage analyses showed an association of Nuclear Distribution Factor E (NDE1) and its homolog NDE-like 1 (NDEL1) with the pathology of mental disorders, the cellular mechanisms remain unclear. I investigated Nde1 (mouse) and Ndel1 (mouse) protein distribution profiles in the adult mouse brain and in cultured neural cells and progenitors. With 50% amino acid sequence similarities, the similarities and differences of their distribution profiles have not been compaired before in adult mouse brain. The purpose of this study is trying to identify the potential roles of Nde1 and Ndel1 in mammalian central nervous system (CNS). This study found that Nde1 and Ndel1 have different but overlapping localization profiles in most parts of the adult mouse CNS. The study also revealed different distribution profiles of Nde1 and Ndel1 in the subventricular zone (SVZ) and the hippocampus, two regions where neurogenesis occurs in the adult brain. The influence of these proteins on neural differentiation was investigated by overexpression in a hippocampal neural stem cell line(HCN-A94). Increasing Nde1 (but not Ndel1) expressions in this neural stem cell line lead to increased neuronal differentiation while decreasing astroglial differentiation. Different subcellular localisation of Nde1 and Ndel1 proteins were found in primary cultured neurons and astrocytes. Nde1 but not Ndel1 was highly localised to the nuclear envelope in both neurons and astrocytes. Ndel1 was strongly distributed to cell processes and growth cones. These findings suggest that Nde1 and Ndel1 may have independent functions during adult neurogenesis and in mature neurons. In the human cortex, NDE1 was found to be distributed in both neurons and astrocytes. It was shown that astrocytic NDE1 have heterogeneous distribution in human cortex. Additionally, NDE1 broadly distribute in multiple human brain regions, which is similar with its distribution in the adult mouse CNS.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Central Nervous System ; Stem cells ; Adult Stem Cells ; Cell Differentiation