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Energy expenditure during stress ulcer formation in vulnerable rats
1Department of Psychiatry, Cornell University Medical College, White Plains, New York.
Insights
Early life stress in rat pups leads to hypothermia and reduced oxidative metabolism when food-deprived. This impaired thermogenesis is not reversed by norepinephrine, suggesting a link to stress ulcer susceptibility.
Area of Science:
- Physiology
- Neuroendocrinology
- Developmental Biology
Background:
- Early life maternal separation in rat pups (postnatal day 15) induces vulnerability to hypothermia and gastric erosion under stress.
- This vulnerability is hypothesized to be linked to decreased oxidative metabolism and impaired thermogenesis.
Purpose of the Study:
- To investigate the association between early life stress (maternal separation) and oxidative metabolism in rat pups.
- To determine if impaired thermogenesis, potentially mediated by norepinephrine (NE), contributes to hypothermia in stressed rat pups.
Main Methods:
- Measured oxygen (O2) consumption in 30-day-old rat pups subjected to maternal separation at postnatal day 15 (15w) or day 21 (21w).
- Assessed O2 consumption during conditions of food availability, food deprivation, and food deprivation with restraint.
- Administered exogenous norepinephrine (NE) to evaluate its effect on O2 consumption in separated and non-separated rats.
Main Results:
- Rat pups separated at day 15 (15w) exhibited significantly lower O2 consumption than controls (21w) when food-deprived or food-deprived and restrained, indicating reduced heat production.
- Administration of exogenous NE failed to restore O2 consumption in 15w rats during food deprivation or restraint, suggesting the issue is not solely due to insufficient NE.
- Oxidative metabolism was decreased in 15w rats under stress, leading to hypothermia.
Conclusions:
- Early life maternal separation in rats impairs oxidative metabolism during stress, resulting in hypothermia.
- The observed hypothermia and reduced oxidative metabolism are not corrected by exogenous norepinephrine, indicating a mechanism beyond simple NE deficiency.
- Decreased oxidative metabolism may underlie the susceptibility to stress ulcers observed in various experimental models following early life stress.
Abstract:
Rat pups separated early from their mothers at day 15 become vulnerable to hypothermia and gastric erosion formation when food deprived and physically restrained on postnatal day 30 (S.H. Ackerman, M. A. Hofer, and H. Weiner, Science Wash. DC. 201: 373-376, 1978, and Gastroenterology 75: 649-654, 1978). We tested the hypothesis that this hypothermia is associated with a decrease in oxidative metabolism. We measured O2 consumption of 30-day-old rat pups that had been previously separated at either day 15 (15w) or day 21 (21w). When food was available, 15w rats used as much O2 as 21w rats. When rats were food deprived or food deprived and restrained, 15w rats used significantly less O2 than 21w rats, implying less heat production. We hypothesized that this decrease in heat production during food deprivation and/or restraint was due to impaired thermogenesis resulting from inadequate release of endogenous norepinephrine (NE), which is a stimulant of brown adipose tissue- (BAT) mediated thermogenesis. To test this hypothesis we administered exogenous NE to 15w to 21w rats. Exogenous NE failed to increase O2 consumption in 21w or 15w rats when injected during either food deprivation or restraint. We concluded that 30-day-old 15w rats have decreased oxidative metabolism during food deprivation and restraint and therefore become hypothermic. This decreased oxidative metabolism does not appear to be attributable to insufficient endogenous NE, since it is not reversed by the addition of exogenous NE. We suggest that a decrease in oxidative metabolism may explain susceptibility to stress ulcers in a number of previously reported experimental models.