碩士 / 國立成功大學 / 生命科學系碩博士班 / 101 / Valproic acid (VPA) is a widely used medicine to treat or prevent epilepsy and bipolar disorder. However, exposure to valproate during pregnancy causes behavioral impairments, like cognitive delay, social interaction, anxious behaviors and interests which is related to symptoms of autistic spectrum disorder. The molecular mechanism remains largely unknown. In our laboratory, we used the model of male rat pups receiving 200 mg/kg of VPA by intraperitoneal injection (ip) at postnatal day 7 (P7). The results from elevated plus-maze test at 2,4 and 6 weeks post injection showed the VPA-injected rats exhibited impaired social interaction and anxiety. Through the open field test, we found that VPA-treated rats displayed an anxious behavior and abnormal locomotion. From the forced swimming test, The VPA-injected rats increase immobility time and depressive behavior. Given the fact that cortex and hippocampus are associated with autistic behaviors, we examined cellular and molecular alterations in the hippocampus of rat at 24 h, week 2, 4, and6. An increased level of acetylated histone H3 was detected at 24 h in hippocampus of rat pups which receiving VPA injection when compared to vehicle-treated rats. BrdU+ -cells or Ki67+ -cells in the hippocampus of rats were also increased at the four observed time point after VPA exposure. In addition, neuronal differentiation gene NeuroD and neuronal migration protein doublecortin were downregulated in the hippocampus of VPA-treated rats at the four detected time points. Olig1 and Olig2 gene expression was also reduced at 24 h after VPA injection, but GFAP mRNA expression was increased in VPA-treated group. Collectively, a bolus of postnatal VPA exposure induced increased cell proliferation and reduced neural differentiation in developing hippocampus of rats with anxiety and depression.
| Identifer | oai:union.ndltd.org:TW/101NCKU5105107 |
| Date | January 2013 |
| Creators | Wei-HuaWang, 王瑋樺 |
| Contributors | Shun-Fen Tzeng, 曾淑芬 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 76 |
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