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Author Contact: jjeong@wesleyan.edu
Local Identifier: Jeong_Jaye_Item_36_1Copies
PID: ir:3043"},{"label":"Author-supplied Keywords","value":["Neural stem and progenitor cells","Subgranular zone","Hippocampus","Neurogenic niche","Hippocampal slice cultures","Adult neurogenesis"]},{"label":"Degree","value":["Master of Arts"]},{"label":"Description","value":"

New neurons are generated throughout life in a process called adult neurogenesis, that occurs in two distinct regions of the mammalian brain, the subventricular zone and the subgranular zone of the hippocampal dentate gyrus. Dysregulation of adult neurogenesis is associated with various neurological disorders, such as temporal lobe epilepsy. Epileptic seizures affect multiple steps in the development of neural progenitor cells and resulting alterations in adult neurogenesis, in turn, contribute to the epileptic disease process. Therefore, adult neurogenesis has been implicated as a promising therapeutic target for seizure related disorders. Prior studies have demonstrated the efficacy of GABAergic interneuron transplantation for suppressing spontaneous seizures and reversing some aspects of aberrant neurogenesis associated with TLE. However, the molecular mechanisms for transplant-mediated suppression of seizure and aberrant neurogenesis are unclear. To address some of these mechanistic gaps, my research focused on establishing an in vitro model of adult neurogenesis in TLE using an organotypic hippocampal slice culture (OHSC) model. While sustained neurogenesis has been well characterized in OHSCs derived from young postnatal mice, whether the SGZ neurogenic niche is preserved in adult hippocampal slice cultures is unclear. Therefore, as a first step, the current thesis focuses on characterizing the neural stem/progenitor cell (NSPC) niche in adult hippocampal slice cultures and investigating how long the NPSCs survive in vitro. Immunohistochemical analyses of the NSPC populations in adult OHSCs at different time points revealed a transient increase in type 2 and type 3 progenitors at 7 days in vitro (DIV), and a significant reduction in the numbers of all progenitor types at 14 and 21 DIV. During the three weeks of cultivation, we also found morphological atrophy of astrocytes, progressive loss of GABAergic interneurons, and gradual dispersion of the suprapyramidal blade of the DG in adult OHSC, suggesting that adult OHSCs lack key factors necessary for NSPCs survival and/or proliferation. Taken together, these findings suggest that the media and environmental oxygen conditions do not maintain the adult neural stem cell niche in the dentate gyrus. Our methods and results provide a framework for future studies that seek to address this technical limitation in the field by systematically manipulating growth factors and media conditions to promote NSPC survival and/or proliferation in adult OHSCs

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