HIPPOCAMPAL DAMAGE ASSOCIATED WITH PROLONGED GLUCOCORTICOID EXPOSURE IN PRIMATES
HIPPOCAMPAL DAMAGE ASSOCIATED WITH PROLONGED GLUCOCORTICOID EXPOSURE IN PRIMATES
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DOI：
10.1523/jneurosci.10-09-02897.1990
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发表时间：
1990-09-01
影响因子：
5.3
通讯作者：
FINCH, CE
中科院分区：
文献类型：
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作者：
SAPOLSKY, RM;UNO, H;FINCH, CE
在实验室大鼠和豚鼠中，糖皮质激素（GC）是应激时分泌的肾上腺类固醇，会损害海马体，并加剧由各种神经损伤引起的海马体损伤。一个悬而未决的问题是，GC 在灵长类动物的海马体中是否也有类似的有害作用。事实上，我们发现，持续和致命的压力与黑长尾猴的海马体优先损伤有关。然而，无法确定伴随这种应激的过量GC分泌是否是破坏因素。本研究探讨了这种可能性。将皮质醇颗粒（灵长类动物的主要 GC）立体定向植入 4 只长尾猴的海马中；对侧海马植入胆固醇颗粒作为对照。一年后进行尸检时，植入皮质醇的一侧发生了优先损伤。在胆固醇方面，4 例中有 2 例观察到轻度细胞层不规则。相比之下，在暴露于皮质醇的海马中，所有病例均具有至少 2 种以下神经病理学标志物：细胞层不规则、树突萎缩、胞体收缩和凝结或核固缩。在某些情况下损伤很严重，并且仅限于 CA3/CA2 细胞区域。这种损伤的解剖学分布以及损伤的细胞特征与在啮齿类海马中GC诱导的毒性和灵长类海马中应激诱导的毒性的情况下观察到的一致。三个观察结果表明，持续接触 GC（无论是由于压力、库欣综合征还是外源性给药）可能会损害人类海马体。
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 hippocampal 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. Three observations suggest that sustained GC exposure (whether due to stress, Cushings syndrome or exogenous administration) might damage the human hippocampus.