Roles of glial cells in neurodegenerative models in Drosophila

• Main Authors: Chia-Yu Liu, 劉佳妤
• Other Authors: Y. Henry Sun
• Format: Others
• Language: en_US
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/85805154175198634534

碩士 === 國立陽明大學 === 生命科學系暨基因體科學研究所 === 101 === Glial cells are essential for supporting neuronal physiological function. Glial cells play roles in the insulation of neuronal activity, metabolic regulation, extracellular homeostasis of ions, and modulation of neurotransmitters. Neurodegenerative diseases show injured neurons often accompanied by glial dysfunction. Several reports also showed expression of these disease proteins in glia enhanced neurotoxicity. However, the contribution of glial cells in neuronal degenerative remains unexplored. I used Drosophila as a model to study the roles of glial cells in neurodegenerative disease. I choose three common neurodegenerative diseases: Alzheimer’s, Parkinson’s and Huntington’s disease to study. When these disease proteins were expressed in photoreceptor cells, they caused neuronal degeneration. I expressed these neurodegenerative disease genes in photoreceptor cells to cause photoreceptor degeneration. Within these genetic backgrounds, I combined repo mutant alleles to make glial cell defect. Repo is a glia-specific protein, and it is required for glial development in Drosophila. Previous study showed that repo mutant could cause photoreceptor cell degeneration due to defect in glial cells. I then checked whether the severity of the eye degeneration phenotype was affected by the repo mutation. I tested ERG and analyzed the retinal thickness and the vacuoles in the lamina and retina layer. Making glial cells defect decreased the amplitude of ERG signals in AD and PD models, indicated that photoreceptor potential was reduced in those two models. And in HD model, ERG amplitude disappeared, this result showed that combined repo mutant made the photoreceptor dysfunction. Second, we measured retinal thickness. The retinal thickness decreased in AD and PD models, but slightly increased in HD model. The vacuolization of retina was rescued by repo mutant in HD model. However, the percentage of vacuole area in lamina did not change in those three neurodegenerative disease models. These results indicated that glial cells defect enhanced reduction of photoreceptor function in three neurodegenerative disease models. Hence, glial cells play supportive role in the aspect of neuronal function in three neurodegenerative disease models. When I analyzed the severity of neuronal degenerative phenotype by morphological phenotype, glial cells also play supportive role in AD and PD models. However, glial cells seem to enhance neuronal degeneration in the aspect of morphological phenotype in HD model flies. These findings provided information that glial cells play different roles in different neurodegenerative diseases. Moreover, the morphological phenotype did not always correlate to functional phenotype specifically in HD model.