- 期刊
Increase in Corticotropin-Releasing Hormone (CRH) in the Central Nervous System Mediates Stressor-Induced Sleep Alterations
中樞CRH之增加調控壓力所誘發之睡眠變化
摘要
目的 我們先前的研究顯示，約束行動（restraint）所產生的壓力會增加老鼠清醒時間，並降低快速動眼期睡眠。而腦室給予促腎上腺皮質激素釋放激素（corticotropin-releasing hormone; CRH）的受體拮抗劑astressin能有效地抑制約束行動所產生的壓力對清醒的影響。我們亦發現在己適應於操作（handling）的老鼠中，約束行動所產生的壓力並不會改變血中皮質固醇（corticosterone）的濃度。基於這些結果，認為約束行動所產生的壓力對睡眠的影響可能不是經由傳統認為的下視丘－腦下垂體－腎上腺皮質體徑（hypothalamic-pituitary-adrenal axis; HPA axia），而是藉由中樞神經中的促腎上腺皮質激素釋放激素。本實驗將進一步證實約束行動所產生的壓力對睡眠的影響是藉由中樞神經中的促腎上腺皮質激素釋放激素。 方法 本實驗中使用未經任何操作的S . D．雄性老鼠。藉由一小時的約束行動後，測量血中皮質固醇的濃度及腦中下視丘、海馬迴、大腦皮質以及腦幹中促腎上腺皮質激素釋放激素先驅物的mRNA 表現。 結果 我們的結果發現，在給予約束行動所產生的壓力後，naïven老鼠血中的皮質固醇明顯增加，而約束行動壓力結束後就回復到原本的濃度範圍內。而腦部下視丘及腦幹中促腎上腺皮質激素釋放激素先驅物的mRNA表現在約束行動時及約束行動後一小時都有顯著地增加。 結論 這些結果更加強我們先前的假說：約束行動所產生的壓力對睡眠的影嚮可能不是經由傳統認為的下視丘－腦下垂體－腎上腺皮質體徑，而是藉由中樞神經中的促腎上腺皮質激素釋放激素。（中台灣醫誌200 尖9 : 80 - 6 )
並列摘要
Objectives. Our previous results demonstrated that an acute stressor increased wakefulness and reduced rapid eye movement sleep (REMS), without altering slow wave sleep (SWS); furthermore, central administration of corticotropin-releasing hormone (CRH) antagonist astressin blocked the increase in wakefulness after stressor. However, stressor in rats well habituated to handling and injection procedures did not alter circulating corticosterone concentrations. Based upon those observations, we hypothesized that under those conditions, central CRH, but not the hypothalamic-pituitary-adrenal (HPA) axis, mediates sleep alterations after stressor. Here we provide further evidence of the increase in prepro-CRH mRNA in the CNS after stressor. Methods. Naive rats were subjected to a 1-hour period of physical restraint. The expression of prepro-CRH mRNA from hippocampus, brainstem, hypothalamus and cortex were measured by ribonucleus protection assay. Total plasma corticosterone was determined by radioimmunoassay. Results. The expression of prepro-CRH mRNA in hypothalamus and brainstem, but not in cortex and hippocampus, had increased after 1-hour of restraint and after 1-hour of recovery postrestraint. Circulating corticosterone concentration rose during the 1-hour period of restraint; however, it returned to its basal concentration after the one-hour recovery period post-restraint. Conclusions. These results suggest that the continuous increase in central CRH, rather than HPA axis activity, mediates the alteration in sleep-wake activity of rats exposed to acute physical restraint. ( Mid Taiwan J Med 2004;9:80-6