碩士 / 國立陽明大學 / 解剖學及細胞生物學研究所 / 103 / Background: Bipolar disorder is a mood disorder comprising alternative depressive and manic phases. There were studies indicating that bipolar disorder was associated with brain structure abnormalities and impaired hippocampal function. Although most studies support that ventral and dorsal hippocampi are in charge of emotional behavior and cognition, respectively, some studies have found that injury in the dorsal hippocampus reduced anxiety and fear and resulted in hyperactivity. The purpose of this study is to clarify weather local lesions in the dorsal hippocampus can result in mania-like symptoms.
Materials and methods: 8-12 week-old male C57BL/6J Narl mice were used for experiments. Using stereotactic technology, needle electrodes were inserted into both dorsal hippocampi (AP: -2.0mm; ML: ± 1.0mm; DV: -2.4mm) of mice under isoflurane anesthesia. Electricity current (1.0mA, 20 seconds) was delivered through the needle electrodes to the lesion group while no electricity was delivered to the sham group. Seven days after the operation, the mice were evaluated with the open field test (OFT) for motility, multiple T-maze (MTM) for spatial memory, freezing test for emotional memory, elevated plus maze (EPM) for anxiety, and forced swim test (FST) for depression. The lesion group was randomly divided to two groups, one for valproic acid (VPA, 200mg/kg/twice/day) and the other for saline treatment for 7 consecutive days. Afterwards, the mice were re-evaluated with the same behavioral methods. The mice were sacrificed and their brains were dissected for measuring the location and size of the stereotactic lesions.
Results: Most of the stereotactic lesions were located in the dorsal dentate gyrus. The lesion group and sham group showed similar learning curve in the MTM, indicating that dorsal dentate gyrus lesions did not impair spatial memory. The lesion group had higher locomotion(P = 0.054) and spent more time in the central area in the OFT (P = 0.045). The lesion group stayed longer duration in the open arms of the EPM (P = 0.007), displayed less immobility in the FST (P = 0.003), and less freezing in response to cue in the freezing test (P = 0.045), indicating less anxiety, depression and fear, respectively. VPA treatment on the lesion group attenuated locomotion (P = 0.003), reduced time in the central area of OFT (P = 0.09) and time in the open arms of EPM (P = 0.03), increased immobility in the FST (P = 0.03), and increased freezing time in the freezing test (P = 0.009).
Conclusion: Lesions in both dorsal hippocampal dentate gyri resulted in mania-like behaviors in mice without impairing spatial memory, and the mania-like behaviors could be attenuated by VPA treatment. This study not only demonstrated the possible pathology of mania but also created a new animal model of mania.
| Identifer | oai:union.ndltd.org:TW/103YM005391017 |
| Date | January 2015 |
| Creators | Chi-Yuan Chang, 張繼元 |
| Contributors | Chung-Jiuan Jeng, Chen-Jee Hong, 鄭瓊娟, 洪成志 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 67 |
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