Impact of Glucose Stress on Dopaminergic Development in Neuronal Cells
| Autor: | Feng-Chuan Tsai, 蔡豐全 |
|---|---|
| Rok vydání: | 2015 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 103 Dysfunction and degeneration of dopaminergic pathways have been associated with different human diseases and Attention-deficit/hyperactivity disorder (ADHD) is one of these psychiatric disorders. A positive correlation between gestational Diabetes Mellitus (DM) and the increased risk of developing ADHD in offspring, has been established in human cohort studies. Here, we examined only one physiological manifestations of DM which is the deficiency in glucose control. We speculated that the continued high glucose concentration can disrupt the dopaminergic pathways, which can occur as the diabetic encephalopathy. Based on this hypothesis, we used Neuro 2a (N2a) and SH-SY5Y, mouse and human neuroblastoma cell lines, respectively, treated with medium containing 2.75, 4.5, and 8.13 g/L glucose to mimic physiological and diabetic conditions. For differentiation, we adapted protocols specifically differentiate N2a and SH-SY5Y towards dopaminergic types. Our study, to best of our knowledge, is the first to attempt to establish the relationship between diabetic glucose stress and its influence on dopaminergic development. We have demonstrated that in both non-differentiated and differentiated stages, glucose stress has adverse effects on the dopaminergic system. In the non-differentiated model, proliferation rate was significantly hindered by glucose stress as early as 24-huous with no apparent cell death detected, whereas in the differentiated model, although TH expression was augmented by high glucose stress, but neurite pruning was enhanced, resulting in significant loss of neurite length. Neuron-derived orphan receptor-1 (NOR-1), a possible transcription factor regulating these responses towards glucose stress, displayed negative association with glucose level in both models and both in cytoplasm and nuclei. Together, we conclude these results may provide a critical window for preventing ADHD and other dopamine-related diseases/disorder by properly controlling the glucose level in a diabetic pregnancy. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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