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Journal of Neuroscience, Vol 10, 3247-3254, Copyright © 1990 by Society for Neuroscience
Hypothalamic-pituitary-adrenal activity in aged, cognitively impaired and cognitively unimpaired rats
AM Issa, W Rowe, S Gauthier and MJ Meaney
Developmental Neuroendocrinology Laboratory, Douglas Hospital, Research Centre, Montreal, Quebec, Canada.
There is a tendency for increased hypothalamic-pituitary-adrenal (HPA)
activity with age in the rat, and the resulting elevations in circulating
glucocorticoid levels have been implicated in the occurrence of hippocampal
pathology and memory deficits. In the experiments reported here, we
examined whether HPA dysfunction is selectively associated with cognitive
impairments in a population of aged rats. Fifty-eight 23-27-month-old male
Long-Evans rats were screened for spatial memory impairments using the
Morris swim maze, and 2 groups of aged animals were selected; aged,
cognitively impaired (AI) animals whose performance was significantly
different (greater than 2 SD) from that of 6-month-old controls and aged,
cognitively unimpaired (AU) animals whose performance was comparable to
that of the young controls (a difference of less than 0.5 SD). Twenty-eight
percent of the animals tested were designated as AI and 20% as AU.
Histological analysis of a subset of these animals showed that, while both
AU and AI animals showed neuron loss in the pyramidal cell fields of the
hippocampus, the loss was significantly greater in the AI animals. The AI
animals showed clear evidence of increased HPA activity. Thus, basal ACTH
and corticosterone levels were significantly higher in the AI animals
compared with both AU animals and young controls, especially during the
dark phase of the cycle. The AI, AU, and young animals exhibited comparable
corticosterone levels during a 20-min immobilization stress; however,
following the termination of the stressor, corticosterone levels in AI
animals were significantly elevated compared with both AU animals and
controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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