碩士 / 國立陽明大學 / 解剖暨細胞生物學研究所 / 97 / Background: Depression is a kind of mental disorder that affects more adults than adolescents and aged people. Depressed patients are more vulnerable to stress and prone to give up, which is similar to learned helplessness in animals induced by inescapable stress. In our preliminary studies we found that young mice were less vulnerable to learned helplessness and helpless mice had higher ApoD mRNA in the hippocampus. In order to clarify the role of ApoD in the pathogenesis of learned helplessness, we studied the relationship among age, vulnerability to stress and the expression of ApoD in the frontal cortex and hippocampus. BDNF (Brain-derived neurotrophic factor) and P11(S100A10) as well known factors in the pathogenesis of depression were studied in parallel.
Methods: Male C57BL/6J mice with a success rate higher than 70% in the screening escape test were used for studies. Intermittent electric foot shocks were given in inescapable stress. Learned helplessness (LH) is defined by an above-70% failure rate in subsequent escape test. Total RNA extracted from the hippocampus and frontal cortex were reversely transcribed to cDNA then quantified using the real-time PCR method. GAPDH was used as internal control to standardize the each sample’s concentration. Inter-assay variation was monitored using a repeatedly assayed sample. The student’s t test and ANOVA test were used to compare group differences.
Results: The LH rate in the 9-week-old, 13-week-old, 24-week-old and 32-week-old mice after 3 sessions’ stress was 35.3%, 69%, 100% and 33.3%, respectively. The LH rate in the 9-week-old and 13-week-old mice after 6 sessions’ stress was 56.3% and 100%, respectively.
The levels of the ApoD mRNA in the frontal cortex (34.7%, 50.3%, 124%) and hippocampus (3%, 26.4%, 55.4%, ) increased with stress in the 9-week-old, 13-week-old and 24-week-old mice, and the increase heightened when stress duration was extended from 3 sessions to 6 sessions in the frontal cortex and hippocampus of the 9-week-old (68.2%, 22.9%) and 13-week-old (151.5%, 100.2%) mice, respectively. Contrarily, the ApoD mRNA in the frontal cortex (-28.3%) and hippocampus (-48.3%) of the 32-week-old mice decreased. There is a correlation between vulnerability to learned helplessness and alterations in ApoD mRNAin the frontal cortex (Spearman's test, R=1.000, P<0.01) and the hippocampus (Spearman's test, R=1.000, P<0.01). There were no significant associations between learned helplessness and the expression of BDNF or P11.
Conclusion: Male C57BL/6J mice’s vulnerability to learned helplessness increases with age from 9 weeks to 24 weeks and decreases at 32 weeks, and the trend correlates with ApoD expression in the frontal cortex and hippocampus. Regulation of ApoD in the frontal cortex and hippocampus may play an important role in the pathogenesis of stress-induced depression.
| Identifer | oai:union.ndltd.org:TW/097YM005391023 |
| Date | January 2009 |
| Creators | Yu-Han Lee, 李玉涵 |
| Contributors | Yn-Ho Huang, Chen-Jee Hong, 黃銀河, 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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