碩士 / 國立清華大學 / 生物資訊與結構生物研究所 / 103 / Epilepsy is a brain disorder that develops spontaneously. Recurring seizures are caused by abnormal neuronal activity in the central nervous system (CNS). The complex etiology of epilepsy is shown to contain multiple causes, including chemical induction, brain injury and genetic factors, which further complicate the analysis. Thus, it is still not possible to predict the occurrence of epileptic seizure due to lack of understanding of its disease mechanism. Previously, we have found the abnormal swimming patterns in traumatic brain injury (TBI) zebrafish resemble the pentylenetetrazol (PTZ)-induced seizure phenotypes. Moreover, expression profiles of several epilepsy-related genes are significantly changed in TBI zebrafish. Therefore, we hypothesize that TBI zebrafish may be used as model to resolve the disease mechanism of brain injury-induced epileptic seizures.
To investigate this hypothesis, we first monitored the behavioral phenotypes of TBI zebrafish and examined the expression profile of known epilepsy markers, c-fos and GABAA receptors gabrg2, in the damaged cerebellum using PCR method. The result indicated 35% of TBI zebrafish displayed seizure-like phenotypes. The seizures-like swimming patterns could be rescued by the administration of valproic acid (VPA), which is a common anti-epileptic drug. Next, we moved to identify genes associated with the TBI-induced seizures by microarray approach. A comparison between TBI and PTZ-treated zebrafishes revealed atf3 and c-jun were significantly up-regulated, implying their potential roles in epileptogenesis. This finding was validated by qPCR assay. We next verified whether TBI may sensitize PTZ-induced seizures via the Atf3 and C-jun signaling pathways. Our data indicated that both Atf3 and C-jun might regulate the development of epileptic seizures as their up-regulations sensitize zebrafish to subsequent PTZ treatment. A comparison between TBI with and without seizures groups further revealed c-fos, atf3 and c-jun were all significantly up-regulated.
In conclusion, we established a TBI model in zebrafish with reproducible epileptic seizures. We have also reported for the first time that Atf3 and C-jun may be involved in the TBI-dependent epileptogenesis. Our findings may be used to develop assays for early diagnosis of TBI-induced epilepsy.
| Identifer | oai:union.ndltd.org:TW/103NTHU5112133 |
| Date | January 2015 |
| Creators | Chen,Ciao Ting, 陳巧婷 |
| Contributors | Chuang,Yung-Jen, 莊永仁 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 53 |
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