| Abstract: | 焦慮是極度壓力下產生的初期反應，其病理機轉可能是透過麩胺酸神經系統(Glutamatergic system)之NMDA (N-methyl-D-aspartate)receptor 參與調節壓力反應。文獻提出，以D-cycloserine(DCS)長時間暴露下導致DCS明顯影響行為的表現；然而，對於DCS生理反應機制仍是未知。本篇研究是將大鼠進行高腳十字迷宮 (Elevated Plus-Maze)行為試驗，以區分為低焦慮組(Low anxiety，LA)及高焦慮組(High anxiety，HA)。並進行強迫游泳試驗(Forced swim test)，觀察大鼠認知及行為上之表現，以評估大鼠憂慮程度。最後抽取大鼠的腦組織蛋白後進行Western blotting相關之蛋白質分析，並以SPSS進行生化和行為關聯性研究。結果發現，高焦慮組隨著DCS處理劑量增加，誘導細胞週期素Cyclin E及Cyclin D1蛋白表現促使G1/S phase之進行，且伴隨著Bcl2的蛋白表現增加。再者，隨著DCS處理劑量增加，亦發現cytochrome C的表現增加。另外，由Fas蛋白表現所引發免疫性細胞凋亡路徑；會協同caspase-3蛋白的表現量增加。本篇論文嘗試建立動物焦慮行為模式，以DCS不同劑量處理後，一併探討腦部紋狀體之蛋白質表現差異，其研究結果有助於對臨床劑量提供一個重要的訊息。
Stress is correlated to the pathophysiology of anxiety, and anxiety is the primary response to stress. The pathophysiology mechanism probably via the glutamatergic N-methyl-d-aspartate (NMDA) receptor is involved in stress responses. It has been demonstrated behavioral effect by long- term exposure to D-cycloserine (DCS). However, still remains unknown the physiological mechanisms of DCS.
The aim of this study, Male Wistar rats, were subjected to the elevated plus-maze (EPM) test divided into low anxiety (LA) and high anxiety(HA) subgroup. Rats received a forced swim test, to observe the cognitive and behavioral effects of DCS depend on the depression level. After excision brain striatum of rats, western blotting assay was used to analysis the striatum proteins, and to study relationship between the biochemistry and behavioral with SPSS.
The present results show that high (HA) anxiety rats following increased by DCS-treated, and up-regulated expression of E- and D1-cyclins, resulting in G1/S stage of cell cycle progression. In addition, showed an increasing trend of Bcl2. Moreover, cytochrome C activity will be forced to enhance after DCS-treated. Interestingly, activating apoptotic signaling pathway by membrane Fas-receptor , and leading to the activation of the downstream caspases, including caspase-3.
In this study, we established an animal's anxious behavior model with the administration of DCS (5, 10, or 30 mg/kg i.p.) or saline. In conclusion, this were probing into expression of difference to the striatum proteins in brain, but also contributes to an important information to clinical therapy. |
