Dokas L A, Schlatter L K, Barr C S
Department of Neurology, Medical College of Ohio, Toledo 43699-0008.
Ann N Y Acad Sci. 1994 Nov 30;746:157-63; discussion 163-5, 178-9. doi: 10.1111/j.1749-6632.1994.tb39227.x.
Cumulative exposure of hippocampal neurons to stress-like levels of corticosterone produces a negative spectrum of cellular alterations from ultrastructural changes to disruption of dendritic morphology and eventual degeneration. An experimental system which adapts itself to characterization of corticosteroid-induced proteins which mediate such effects is the hippocampal slice incubated in the presence of a radiolabeled amino acid following treatment of rats with corticosterone. The most consistently observed response to elevated corticosterone levels produced by exogenous injection is synthesis of a hippocampal cytosolic protein which has characteristics of glycerol phosphate dehydrogenase. Because synthesis of this protein is enhanced with a short latency as serum corticosterone levels are increased and terminated quickly upon re-establishment of basal conditions, it serves as a valid biological marker of the response of the hippocampus to short-term stress. In contrast, alterations in synthesis of other proteins following corticosterone treatment only become apparent under defined conditions or after chronic treatment. For example, steroid-inhibited synthesis of a hippocampal protein with an approximate molecular weight of 25,000 is only observed when slices are incubated at an elevated temperature. Such negative changes may represent loss of adaptive responses that protect the neuron from damage by cellular insults.
海马神经元累积暴露于应激水平的皮质酮会产生一系列负面的细胞改变，从超微结构变化到树突形态破坏，最终导致神经元退化。一种适用于表征介导此类效应的皮质类固醇诱导蛋白的实验系统，是在用皮质酮处理大鼠后，将海马切片置于放射性标记氨基酸存在的条件下进行孵育。对外源注射导致的皮质酮水平升高最一致观察到的反应，是合成一种具有甘油磷酸脱氢酶特征的海马胞质蛋白。由于随着血清皮质酮水平升高，这种蛋白质的合成会在短时间内增强，而在恢复基础条件后会迅速终止，因此它可作为海马对短期应激反应的有效生物学标志物。相比之下，皮质酮处理后其他蛋白质合成的改变仅在特定条件下或长期处理后才会显现。例如，只有当切片在升高的温度下孵育时，才会观察到一种分子量约为25,000的海马蛋白的类固醇抑制合成。此类负面变化可能代表着保护神经元免受细胞损伤的适应性反应的丧失。
