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Journal of Neuroscience, Vol 10, 2897-2902, Copyright © 1990 by Society for Neuroscience
Hippocampal damage associated with prolonged glucocorticoid exposure in primates
RM Sapolsky, H Uno, CS Rebert and CE Finch
Department of Biological Sciences, Stanford University, California 94305.
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.
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