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Effects of acute and repeated exposure to stress on the hypothalamo-pituitary-adrenocortical activity in mice during
F R D'Amato1, S Cabib, S Puglisi-Allegra
1Istituto di Psicobiologia e Psicofarmacologia (CNR), Rome, Italy.
Insights
Mild stress, like novel odors, activates the hypothalamo-pituitary-adrenocortical (HPA) axis in developing mice. This response is consistent across various ages, showing no habituation to the stressor.
Area of Science:
- Neuroscience
- Endocrinology
- Developmental Biology
Background:
- The hypothalamo-pituitary-adrenocortical (HPA) axis regulates stress response.
- Understanding HPA axis development in early life is crucial for identifying developmental vulnerabilities.
Purpose of the Study:
- To investigate the HPA axis response to a mild stressor in mice during postnatal development.
- To determine if repeated exposure to the stressor leads to habituation.
Main Methods:
- Assessing plasma corticosterone levels in mouse pups at postnatal days 8, 10, 12, and 14.
- Utilizing mild stressors: novel odor exposure (clean bedding), maternal separation, and isolation.
- Evaluating maternal corticosterone levels and potential transfer via milk.
Main Results:
- Exposure to a novel odor (clean bedding) significantly elevated plasma corticosterone in pups at Days 12 and 14.
- Younger pups (Day 8) showed robust HPA response when isolated without bedding, indicating developmental capacity.
- Repeated exposure to clean bedding did not lead to habituation of the corticosterone response in 14-day-old mice.
- Maternal corticosterone response habituated with repeated pup removal, ruling out milk-borne transfer as a factor.
Conclusions:
- A 15-minute exposure to clean bedding is a non-invasive method to elicit HPA axis response in developing mice.
- The HPA axis is responsive to this mild stressor across a wide age range without habituation.
- Maternal stress response habituation suggests pups are not significantly influenced by milk-borne corticosterone during repeated manipulations.
Abstract:
Hypothalamo-pituitary-adrenocortical (HPA) response to a mild stressful procedure was investigated in mice at Days 8, 10, 12, and 14 of postnatal development. Pups that were removed from the dam and exposed to a novel odor (clean bedding) for 15 min showed higher plasma corticosterone levels than pups whose mother was removed from the cage for 15 min or unhandled pups at all ages, although statistically significant differences were only evident at Days 12 and 14. Lower HPA axis responding in younger mice was not due to immaturity since 8-day-old mice showed a significant and larger increase of plasma corticosterone levels when separated from the mother and isolated from littermates in the absence of bedding. Mice daily exposed to clean bedding (15 min) for the first 13 days of life did not show reduced plasma corticosterone response when reexposed to the stressor at 14 days of age. Conversely, increased plasma corticosterone levels in dams in response to removal of pups was not detectable after repeated exposure to this manipulation (14 days) regardless of the procedure their pups were submitted to, thus ruling out a role of maternal corticosterone passing through the milk on which the pups were fed. These results demonstrate that 15 min exposure to clean bedding is a noninvasive procedure able to elicit HPA axis response in developing mice over a wide age range without producing habituation.