Uno H, Tarara R, Else J G, Suleman M A, Sapolsky R M
Regional Primate Research Center, University of Wisconsin, Madison 53715-1299.
J Neurosci. 1989 May;9(5):1705-11. doi: 10.1523/JNEUROSCI.09-05-01705.1989.
Sustained exposure to glucocorticoids (GCs), adrenal hormones secreted during stress, can cause neural degeneration in the rat. This is particularly so in the hippocampus, a principal neural target site for GCs, in which GCs can exacerbate the rate of neuron death during normal aging, as well as the severity of neuronal damage after various neurological insults. Thus, stress can be a potent modulator of hippocampal degeneration in the rat. The present report suggests a similar association in the primate. Eight vervet monkeys, housed in a primate center in Kenya, that had died spontaneously from 1984 to 1986, were found at necropsy to have multiple gastric ulcers; a retrospective, neuropathological study was then done of this opportunistic population. Compared with controls euthanized for other research purposes, ulcerated monkeys had marked hippocampal degeneration that was apparent both quantitatively and qualitatively, and both ultrastructurally and on the light-microscopic level. Minimal damage occurred outside the hippocampus. Damage was unlikely to have been due to an agonal or post-mortem artifact. Instead, ulcerated monkeys appear to have been subject to sustained social stress, perhaps in the form of social subordinance in captive breeding groups: most came from social groups, had significantly high incidences of bite wounds at necropsy, and had hyperplastic adrenal cortices, indicative of sustained GC release. Moreover, the specific hippocampal cell fields damaged in ulcerated animals matched those damaged by GCs in the rodent hippocampus. Thus, this represents the first evidence suggesting that sustained stress, via GC hypersecretion, might be neurodegenerative in the primate.
持续暴露于糖皮质激素（GCs），即应激期间分泌的肾上腺激素，可导致大鼠神经退变。在海马体中尤其如此，海马体是GCs的主要神经靶位点，在其中GCs可加剧正常衰老过程中的神经元死亡速度，以及各种神经损伤后的神经元损伤严重程度。因此，应激可能是大鼠海马体退变的有力调节因素。本报告表明在灵长类动物中也存在类似关联。对1984年至1986年期间在肯尼亚一个灵长类动物中心自然死亡的8只绿猴进行尸检时发现，它们患有多处胃溃疡；随后对这一机会性群体进行了回顾性神经病理学研究。与因其他研究目的而安乐死的对照组相比，患有溃疡的猴子海马体有明显退变，在数量和质量上、超微结构和光学显微镜水平上均很明显。海马体以外的部位损伤极小。损伤不太可能是濒死期或死后假象所致。相反，患有溃疡的猴子似乎遭受了持续的社会应激，可能是以圈养繁殖群体中的社会从属地位的形式：大多数来自社会群体，尸检时咬伤发生率显著较高，肾上腺皮质增生，表明GCs持续释放。此外，患有溃疡的动物中受损的特定海马体细胞区域与啮齿动物海马体中被GCs损伤的区域相匹配。因此，这代表了首个证据，表明持续应激通过GCs分泌过多可能在灵长类动物中具有神经退行性作用。
