Related Experiment Videos
Effect of Interleukin-1beta on Pituitary-Adrenal Responses and Body Weight in Neonatal Rats: Interaction with
1Stanford University School of Medicine, Department of Psychiatry & Behavioral Sciences, Primate Facility 7-930T, Stanford, CA 94305-5095, U.S.A.
Insights
Maternal deprivation alters infant rat hypothalamic-pituitary-adrenal (HPA) axis responses to interleukin-1beta (IL-1beta) in an age-dependent manner. These changes are influenced by maternal contact, affecting stress hormone levels and food intake.
Area of Science:
- Neuroendocrinology
- Developmental Neuroscience
- Immunology
Background:
- The infant rat hypothalamic-pituitary-adrenal (HPA) axis is typically hyporesponsive during postnatal days 4-14 (stress hyporesponsive period, SHRP).
- Interleukin-1beta (IL-1beta) can activate the HPA axis even during the SHRP.
- Maternal deprivation is known to disrupt the normal HPA axis development and responsiveness.
Purpose of the Study:
- To investigate the interaction between maternal deprivation and IL-1beta administration on the HPA axis at different developmental ages (pnd 6, 12, 18).
- To examine the influence of maternal contact post-IL-1beta injection on HPA axis activity in deprived pups.
- To understand the age-dependent effects of IL-1beta and maternal deprivation on stress hormone (ACTH, CORT) and immune responses.
Main Methods:
- Infant rats (pnd 6, 12, 18) underwent 24-hour maternal deprivation followed by intraperitoneal injection of recombinant human IL-1beta (rhIL-1beta) or vehicle.
- Plasma ACTH and corticosterone (CORT) levels were measured at various time points post-injection.
- Maternal contact was provided post-injection in some groups.
- Plasma concentrations of endogenous rat IL-1beta and body weight changes (food intake) were also assessed.
Main Results:
- Maternal deprivation modulated IL-1beta-induced HPA axis activation in an age-dependent manner: greater response at pnd 6, quicker at pnd 12, and suppressed at pnd 18.
- Maternal contact post-injection differentially affected ACTH and CORT responses across ages, sometimes augmenting and sometimes suppressing them.
- Differences in HPA response were not attributed to altered immune responses to IL-1beta; IL-1beta reduced food intake in deprived pups at all ages.
Conclusions:
- Maternal deprivation significantly alters the developing HPA axis's sensitivity to IL-1beta, with effects varying by age and maternal care.
- IL-1beta activates the HPA axis through pathways beyond direct hypothalamic action, particularly in the context of early life stress.
- These findings highlight the critical role of early life experiences and immune signaling in shaping neuroendocrine stress responses.
Abstract:
The hypothalamic-pituitary-adrenal (HPA) axis of the infant rat is normally hyporesponsive during postnatal days (pnd) four to fourteen. This interval is termed the stress hyporesponsive period (SHRP). The HPA axis, however, does respond to selective stimuli, such as interleukin-1beta (IL-1beta) during this period. Furthermore, maternal deprivation has been shown to alter the system so that it is responsive to mild stimuli. The present studies examined the interaction between 24 h of maternal deprivation and intraperitoneal administration of recombinant human (rh) IL-1beta (4 µg/kg) at 3 ages (i.e., pnd 6, 12, 18) during or after the SHRP. The results demonstrate that maternal deprivation modifies the response of the HPA axis induced by IL-1beta in an age-dependent fashion: 1) a greater response at pnd 6; 2) a quicker response at pnd 12; and 3) a suppressed response pattern at pnd 18. Moreover, these responses across ages differ as a function of maternal contact postinjection: 1) deprivation augments the ACTH and CORT response and maternal contact postinjection further augments this response at pnd 6; 2) deprivation increases the ACTH and CORT response to vehicle and the CORT response to IL-1beta in 12 day-old pups and the mother has a modest inhibitory effect; and 3) at pnd 18 deprivation leads to lower ACTH concentrations, but higher overall CORT levels and maternal contact postinjection effectively suppresses both the ACTH and CORT response to IL-1. These differences in the HPA response do not appear to be due to differences in the immune response. Plasma concentrations of endogenous rat IL-1beta determined 1 and 2 h after injection of rhIL-1beta were not modified by deprivation and were reduced at pnd 18 compared to pnd 6 and 12 in NDEP pups. Finally, IL-1beta reduced food intake, as reflected by a decrease in body weight, in deprived pups at all 3 ages. The findings in the present experiments suggest that there are additional pathways through which IL-1beta can act on the CNS to activate the HPA axis besides direct action at the hypothalamus.