Effect of Deprenyl on Memory Impairment in the Stressed Mice
| Autor: | Chi-Hong Chang, 張啟宏 |
|---|---|
| Rok vydání: | 2008 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 96 Backgrounds：Stress is generally defined in biological systems as any condition that seriously perturbs the physiological/psychological homeostasis of an organism. In humans, a number of stress-associated conditions have been identified; e.g. hypertension, diabetes, gastric-intestinal ulceration, depression, anxiety and posttraumatic stress disorder (PTSD). Some studies indicate that stress will damage the cells in hippocampus and prefrontal cortex, and further damage the memory functions of the brain. The prefrontal cortex plays an important role in the integration of cognitive and affective behavior and spatial working memory. Many reports indicate that chronic stress induces impairment of spatial working memory because of prefrontal dopaminergic dysfunction. Deprenyl is a selective irreversible inhibitor of monoamine oxidase-B（MAO-B Inhibitor）and can increase dopamine concentration in brain. Both stress and dopamine can induce c-fos, a cellular immediate-early gene, expression. cAMP-response element binding protein (CREB) is a transcription factor, and many researches indicate that CREB phosphorylation (pCREB) is involved in memory processes. Besides, CREB is also involved in addiction and depression. In this study, we aimed to investigate whether deprenyl can improve the stress-induced working memory impairment using c-Fos and pCREB immunohistochemical labeling as coindicators. Methods：Male C57BL/6JNarl mice (8-week age) were divided into: 1) saline control group (N=6); 2) saline-stress group (N= 10); 3) fluoxetine -stress group (N= 10); deprenyl (10 mg)-stress group(N=10); and deprenyl (1 mg)-stress group（N=10）. Mice will receive different drug treatments and/or 300 inescapable foot-shocks according to their group for three days. After that, all mice will receive both 3 day’s- T-maze training and 3 day’s- T-maze memory test. Another group of mice were received the same drug treatment and/or 300 inescapable foot-shocks according to their group for three days and were immediately deeply anesthetized and the brain removed and cryostated for c-Fos and pCREB immunohistochemical studies among brain regions, such as the hippocampus (CA1, CA3 and DG), medial prefrontal cortex (MPC) and hypothalamic paraventricular nuclei, etc. Results：Our behavioral result indicated that the correct percentage of T-maze test of the deprenyl (10 mg) group mice showed significant increase as compared with that of the saline+stress group mice both in the day 2 and day 3 performance. The deprenyl (1 mg) only showed significant increase in the day 3. In addition, the Fluoxetine (10 mg) group mice showed significant increase in all the 3 day’s tests. The c-Fos results showed that the number of the positive neurons in the prefrontal cortex, CA1, CA3 and DG of the deprenyl mice were significant increased as compared to that of the saline+stress mice.However, tha c-Fos positive cells in the hypothalamic paraventricular nuclei of the deprenyl mice were significant decreased as compared to that of the saline+stress mice Conclusions：Treatment with deprenyl or fluoxetine could reduce the spatial working memory impairment in stressed mice, and the functional significance of c-Fos and pCREB expression in both the memory and sress related areas in mice of each group in this research remain te be elucidated. |
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