碩士 / 國立成功大學 / 藥理學研究所 / 96 / Most human neonates experience temporary physiological jaundice, due to immaturity of hepatic conjugation and transport processes for bilirubin. However, in some infants, plasma bilirubin levels can increase dramatically owing to the excessive production or enterohepatic circulation of bilirubin, and the delayed maturation of, or inherited deficiencies in the conjugation of bilirubin. Some neonates with severe hyperbilirubinemia develop bilirubin encephalopathy, in which multifocal deposition of bilirubin in selected brain regions results in temporary or permanent impairment of brain function. In this study, we investigate whether chronic exposure of developing rat organotypic hippocampal slice cultures to unconjugated bilirubin (UCB) alters the synaptic organization and the induction of long-term synaptic plasticity. We have found that treatment of the developing rat organotypic hippocampal slice cultures to UCB 1 or 10 μM for 24 h or 48 h can impair the induction of both CA1 long-term potentiation (LTP) and long-term depression (LTD) in a time- and concentration-dependent manner. Hippocampal slice cultures stimulated with UCB showed no changes in the secretion profiles of IL-1beta and TNF-alpha or the propidium ioide (PI) uptake. UCB treatment produced a significant decrease in the levels of NR1, NR2A and NR2B subunits of NMDA receptors through a calpain-mediated proteolysis mechanism. Pretreatment of the hippocampal slice cultures with NMDA receptor antagonist or calpain inhibitors effectively prevented the UCB-induced impairment of LTP and LTD. Finally, chronic UCB treatment also decrease the number of dendrite spine in the hippocampal slice cultures. These results indicate that NMDA receptor receptor-cleavage by calpain may play critical roles in mediating the UCB-induced impairment of long-term synaptic plasticity in the developing hippocampus. We provide a significant advance in understanding the chronic effects of UCB exposure on neuronal functions.
| Identifer | oai:union.ndltd.org:TW/096NCKU5550002 |
| Date | January 2008 |
| Creators | Fang-Yu Chang, 張芳瑀 |
| Contributors | Kuei-Sen Hsu, 許桂森 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 106 |
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