Sapolsky R M, Uno H, Rebert C S, Finch C E
Department of Biological Sciences, Stanford University, California 94305.
J Neurosci. 1990 Sep;10(9):2897-902. doi: 10.1523/JNEUROSCI.10-09-02897.1990.
In the laboratory rat and guinea pig, glucocorticoids (GCs), the adrenal steroids that are secreted during stress, can damage the hippocampus and exacerbate the hippocampal damage induced by various neurological insults. An open question is whether GCs have similar deleterious effects in the primate hippocampus. In fact, we showed that sustained and fatal stress was associated with preferential hippocampal damage in the vervet monkey; however, it was not possible to determine whether the excessive GC secretion that accompanied such stress was the damaging agent. The present study examines this possibility. Pellets of cortisol (the principal GC of primates) were stereotaxically implanted into hippocampi of 4 vervet monkeys; contralateral hippocampi were implanted with cholesterol pellets as a control. One year later at postmortem, preferential damage occurred in the cortisol-implanted side. In the cholesterol side, mild cell layer irregularity was noted in 2 of 4 cases. By contrast in the cortisol-exposed hippocampi, all cases had at least 2 of the following neuropathologic markers: cell layer irregularity, dendritic atrophy, soma shrinkage and condensation, or nuclear pyknosis. Damage was severe in some cases, and was restricted to the CA3/CA2 cellfield. This anatomical distribution of damage, and the cellular features of the damage agree with that observed in instances of GC-induced toxicity in the rodent hippocampus, and of stress-induced toxicity in the primate hippocampus. These observations suggest that sustained GC exposure (whether due to stress, Cushings syndrome or exogenous administration) might damage the human hippocampus.
在实验大鼠和豚鼠中，糖皮质激素（GCs），即应激期间分泌的肾上腺类固醇，可损害海马体，并加剧由各种神经损伤诱导的海马体损伤。一个悬而未决的问题是，GCs在灵长类动物海马体中是否具有类似的有害作用。事实上，我们发现持续的致命应激与绿猴海马体的优先损伤有关；然而，无法确定伴随这种应激的GC过度分泌是否就是损伤因子。本研究探讨了这种可能性。将皮质醇（灵长类动物的主要GC）丸剂立体定向植入4只绿猴的海马体中；对侧海马体植入胆固醇丸剂作为对照。一年后尸检时，皮质醇植入侧出现了优先损伤。在胆固醇植入侧，4例中有2例出现轻度细胞层不规则。相比之下，在暴露于皮质醇的海马体中，所有病例至少有以下两种神经病理学标志物：细胞层不规则、树突萎缩、胞体收缩和凝聚或核固缩。在某些病例中损伤严重，且局限于CA3/CA2细胞区域。这种损伤的解剖分布以及损伤的细胞特征与在啮齿动物海马体中GC诱导的毒性以及灵长类动物海马体中应激诱导的毒性中观察到的情况一致。这些观察结果表明，持续暴露于GC（无论是由于应激、库欣综合征还是外源性给药）可能会损害人类海马体。
