Elizabeth Peloso

Foster Children’s Diurnal Production of Cortisol: An Exploratory Study

Young children in foster care have often experienced inadequate early care and separations from caregivers. Preclinical studies suggest that early inadequate care and separations are associated with long-term changes in regulation of the hypothalamic-pituitary-adrenal (HPA) axis. In this study, the daytime pattern of cortisol production was examined among 55 young children who had been placed into foster care and 104 children who had not. Saliva samples were taken at wake-up, in the afternoon, and bedtime for 2 days. Average salivary cortisol values for each time of day were computed. A group (foster vs. comparison) time (morning, afternoon, night) interaction emerged, reflecting less decline in levels across the day for foster than comparison children. Daytime patterns were categorized as typical, low, or high. Children who had been in foster care had higher incidences of atypical patterns of cortisol production than children who had not. These differences suggest that conditions associated with foster care interfere with children’s ability to regulate neuroendocrine functioning.

A preliminary study of medial temporal lobe function in youths with a history of caregiver deprivation and emotional neglect

Previous research findings have linked caregiver deprivation and emotional neglect with sensitivity to threatening cues. The present preliminary study investigated whether dysfunctions of the medial temporal lobe could underlie these associations. Using fMRI, we measured medial temporal lobe responses to emotional faces (angry, fearful, happy, neutral) among 30 youths. Eleven of the youths had a history of caregiver deprivation and emotional neglect. Attention states (i.e., attention to anger, fear, or physical attributes, or passive viewing) were systematically manipulated. Relative to comparison youths, youths with a history of caregiver deprivation and emotional neglect showed significantly greater left amygdala and left anterior hippocampus activation during the processing of threatening information. To our knowledge, these findings are the first to demonstrate altered medial temporal lobe function during the processing of threat cues in youths with a history of caregiver deprivation and emotional neglect.

Basal and IL-1β-stimulated cytokine and neuropeptide mRNA expression in brain regions of young and old Long–Evans rats

Young and old Long-Evans rats respond with fevers of equal magnitude and duration to the brain administration of interleukin-1beta (IL-1beta). Here, we characterized brain regional mRNA expression of cytokine and neuropeptide components in response to the brain administration of IL-1beta. We used specific and highly sensitive RNase protection assays to determine mRNA changes for IL-1beta, IL-1 receptor type I (IL-1RI), IL-1R accessory proteins I and II (IL-1R AcP I and II), IL-1 receptor antagonist (IL-1Ra), transforming growth factor-beta1 (TGF-beta1), glycoprotein 130 (gp 130), leptin receptor (OB-R), neuropeptide Y (NPY) and pro-opiomelanocortin (POMC) in the cerebellum, parieto-frontal cortex, hippocampus, hypothalamus, and midbrain of male young (3-5 months) and old (24-26 months) Long-Evans rats. In both young and old rats, IL-1beta induced a significant up-regulation of cerebellar IL-1Ra, IL-1RI, and TGF-beta1 mRNAs; hippocampal TGF-beta1 mRNA; hypothalamic IL-1beta, IL-1Ra, TGF-beta1, and gp 130 mRNAs; and midbrain IL-1beta and TGF-beta1 mRNAs. There were no age-related differences in any cytokine mRNA levels under basal or IL-1beta-stimulated conditions. Levels of hypothalamic POMC mRNA were different between age groups under basal and stimulated conditions. IL-1R AcP I and leptin receptor did not change in any brain region from either young or old rats, suggesting specificity of transcriptional changes. The data show that old Long-Evans rats are not defective in their capacity to develop an appropriate cytokine response to the brain administration of IL-1beta. The implications of these findings for neuroimmunological-neuroinflammatory and neurotoxic/neurodegenerative processes are discussed.

Incentive effect on inhibitory control in adolescents with early-life stress: an antisaccade study

OBJECTIVE Early-life stress (ES) such as adoption, change of caregiver, or experience of emotional neglect may influence the way in which affected individuals respond to emotional stimuli of positive or negative valence. These modified responses may stem from a direct alteration of how emotional stimuli are coded, and/or the cognitive function implicated in emotion modulation, such as self-regulation or inhibition. These ES effects have been probed on tasks either targeting reward and inhibitory function. Findings revealed deficits in both reward processing and inhibitory control in ES youths. However, no work has yet examined whether incentives can improve automatic response or inhibitory control in ES youths. METHOD To determine whether incentives would only improve self-regulated voluntary actions or generalize to automated motoric responses, participants were tested on a mixed eye movement task that included reflex-like prosaccades and voluntary controlled antisaccade eye movements. Seventeen adopted children (10 females, mean age 11.3 years) with a documented history of neglect and 29 typical healthy youths (16 females, mean age 11.9 years) performed the mixed prosaccade/antisaccade task during monetary incentive conditions or during no-incentive conditions. RESULTS Across both saccade types, ES adolescents responded more slowly than controls. As expected, control participants committed fewer errors on antisaccades during the monetary incentive condition relative to the no-incentive condition. By contrast, ES youths failed to show this incentive-related improvement on inhibitory control. No significant incentive effects were found with prepotent prosaccades trials in either group. Finally, co-morbid psychopathology did not modulate the findings. CONCLUSIONS These data suggest that youths with experience of early stress exhibit deficient modulation of inhibitory control by reward processes, in tandem with a reward-independent deficit in preparation for both automatic and controlled responses. These data may be relevant to interventions in ES youths.

Suprachiasmatic Nuclei Lesions Do Not Eliminate Homeostatic Thermoregulatory Responses in Rats

Electrolytic lesions aimed at the suprachiasmatic nuclei (SCN) were made in male Long-Evans rats. Body temperature (Tb), activity, and drinking were monitored continuously in a 12-h light:12-h dark (12:12 LD) cycle at an ambient temperature of 23°C. Large SCN lesions eliminated activity and drink ing rhythms and abolished or reduced the circadian rhythm of Tb. The Tb responses of the rats were measured in L after exposure to cold and injection of lipopolysaccharide (LPS), a fever-producing drug, and in both L and D during a 30-min exposure to a novel cage. Rats with SCN lesions (SCNX) maintained their Tb as well as did controls during 2-h exposure to 2°C. They also showed the expected increases in Tb in response to novelty and LPS. Nevertheless, there were differences between SCNX rats and other rats. When measured 9 h after LPS injection, SCNX rats had lower Tb in D than did sham-lesioned or intact rats or rats with lesions that missed the SCN. This is not surprising; the Tb of SCNX rats does not go as high as that of intact rats in D. However, it was surprising that at night SCNX rats increased their Tb in response to novelty (lights on in the test situation), whereas normal rats did not. For some reason, light inhibits the Tb rise to novelty in normal rats but does not do so in rats with SCN lesions.

LPS fever in old rats depends on the ambient temperature

In earlier work, we found that following lipopolysaccharide (LPS) injection at an ambient temperature (Ta) of 23 degrees C, old rats developed blunted fevers compared with those of young rats. However, the old rats did become febrile if placed in a thermally graded alleyway: they spent more time in the warm end of the gradient and developed a significantly higher body temperature (Tb) than they did following saline injections. In the present experiments, we maintained old and young rats for 3 days at 20 or 31 degrees C (the Ta preferred by the old rats given LPS). After LPS (50 microg/kg ip), the young rats developed equivalent fevers at both Tas. The old rats developed fevers that were equivalent to those of the young rats at 31 degrees C. At 20 degrees C, their fever was significantly lower. These results suggest that Ta plays a decisive role in the ability of old rats to mount febrile responses.

Stress-Induced Hyperthermia Depends on Both Time of Day and Light Condition

Rats placed in an environment other than their home cage increase their body temperature (Tb) by more than 1 °C. This stress-induced hyperthermia is considered to be a fever, in the sense that the Tb rise seems to reflect an upward shift in the level of regulated Tb (set point). The circadian rhythm of Tb also reflects changes in set point. One might therefore expect to see differences in response to such stress during various phases of the light-dark (LD) cycle as Tb fluctuates between L and D. To test this, 3- to 6-month-old male Long-Evans rats were taken from their home cages (12:12 LD) and placed individually in a Plexiglas container for 30 min. Tb and activity were measured via telemetry. In the first experiment, rats were placed in the container during day (from 1 to 3 h after lights on) and night (from 1 to 3 h after lights off), with light on or off during the test. There was a significant Tb rise in response to placement in the container at all times except when the rats were tested during the night with light on in the container; in that condition there was no Tb rise. In the second experiment, the authors determined that 30 min of light in the home cage before the test did not affect Tb: If the light was on in the test situation, hyperthermia was inhibited, and if it was off, hyperthermia was as high as control levels. In the third experiment, to determine whether this effect was time dependent, the test was performed at 4-h intervals, with light on or off during the test. The strongest inhibiting effect of light was in early night. In the fourth experiment, the authors turned the lights on during early night while the rats were in their home cages. This reduced their Tb significantly by less than 0.3 °C. The authors conclude that both clock time and light condition during testing are factors affecting the Tb rise in response to stress.

Cytokine-induced fever in obese (fa/fa) and lean (Fa/Fa) Zucker rats

In earlier work, we reported that genetically obese ( fa/ fa) Zucker rats exhibited significantly greater anorexia than did lean ( Fa/ Fa) Zucker rats to intracerebroventricular infusion of interleukin (IL)-1β. Here, we investigated the fever response of obese ( fa/ fa) and lean ( Fa/ Fa) Zucker rats to intracerebroventricular microinfusion of IL-1β as well as to the following other cytokines: IL-2, IL-6, and tumor necrosis factor-α (TNF-α). Core body temperature was monitored by a radiotelemetry system in freely moving rats. The results show that 1) both IL-1β and IL-6 induce fevers in obese and lean rats; 2) IL-1β induces a significantly higher fever response in obese rats than it does in lean rats; 3) IL-6 induces a significantly higher fever response in lean rats than it does in obese rats; 4) IL-2 induces a moderate fever response in lean but not obese rats; 5) TNF-α induces a similar fever response in obese and lean rats; and 6) the fevers induced by each effective cytokine have different time courses. Thus obese ( fa/ fa) and lean ( Fa/ Fa) Zucker rats show differential responsiveness to the intracerebroventricular microinfusion of various classes of cytokines. This suggests that genetic obesity in the fa/fa Zucker rat is associated with differential cytokine action on thermoregulatory mechanisms.In earlier work, we reported that genetically obese (fa/fa) Zucker rats exhibited significantly greater anorexia than did lean (Fa/Fa) Zucker rats to intracerebroventricular infusion of interleukin (IL)-1beta. Here, we investigated the fever response of obese (fa/fa) and lean (Fa/Fa) Zucker rats to intracerebroventricular microinfusion of IL-1beta as well as to the following other cytokines: IL-2, IL-6, and tumor necrosis factor-alpha (TNF-alpha). Core body temperature was monitored by a radiotelemetry system in freely moving rats. The results show that 1) both IL-1beta and IL-6 induce fevers in obese and lean rats; 2) IL-1beta induces a significantly higher fever response in obese rats than it does in lean rats; 3) IL-6 induces a significantly higher fever response in lean rats than it does in obese rats; 4) IL-2 induces a moderate fever response in lean but not obese rats; 5) TNF-alpha induces a similar fever response in obese and lean rats; and 6) the fevers induced by each effective cytokine have different time courses. Thus obese (fa/fa) and lean (Fa/Fa) Zucker rats show differential responsiveness to the intracerebroventricular microinfusion of various classes of cytokines. This suggests that genetic obesity in the fa/fa Zucker rat is associated with differential cytokine action on thermoregulatory mechanisms.

Interleukin-1β-induced fever in young and old Long-Evans rats

Aging is associated with a blunted or absent fever response to naturally occurring infections or to the peripheral administration of bacterial products and proinflammatory cytokines, including interleukin-1β (IL-1β). Whether old rats also exhibit an attenuated fever response when challenged with direct brain administration of IL-1β is unknown. Here we investigated the fever response of young (3-5 mo) and old (24-26 mo) Long-Evans rats to the intracerebroventricular microinfusion of IL-1β. Core body temperature was monitored by telemetry in freely moving rats. Intracerebroventricularly administered IL-1β induced comparable increases in body temperature in young and old Long-Evans rats. In the two groups, IL-1β-induced fever was similar both in latency to peak fever and maximal fever response, whether the cytokine was administered 2 h after lights on or just before lights off. These data show that old Long-Evans rats are not defective in their capacity to develop a fever in response to brain administration of IL-1β.Aging is associated with a blunted or absent fever response to naturally occurring infections or to the peripheral administration of bacterial products and proinflammatory cytokines, including interleukin-1beta (IL-1beta). Whether old rats also exhibit an attenuated fever response when challenged with direct brain administration of IL-1beta is unknown. Here we investigated the fever response of young (3-5 mo) and old (24-26 mo) Long-Evans rats to the intracerebroventricular microinfusion of IL-1beta. Core body temperature was monitored by telemetry in freely moving rats. Intracerebroventricularly administered IL-1beta induced comparable increases in body temperature in young and old Long-Evans rats. In the two groups, IL-1beta-induced fever was similar both in latency to peak fever and maximal fever response, whether the cytokine was administered 2 h after lights on or just before lights off. These data show that old Long-Evans rats are not defective in their capacity to develop a fever in response to brain administration of IL-1beta.

Prostaglandin E2-Induced Fever in Young and Old Long–Evans Rats

Aging is associated with a blunted or absent fever response to naturally occurring infections or to the peripheral administration of bacterial products and proinflammatory cytokines. We have recently shown that old Long-Evans rats are not defective in their capacity to develop a fever in response to brain administration of interleukin-1beta (IL-1beta). Here, we investigated the fever response of young (3-5-month) and old (24-26-month) Long-Evans rats to the intracerebroventricular (i.c.v.) microinfusion of prostaglandin E2 (PGE2), a final common mediator for the production of fever in the brain. Core body temperature was monitored by telemetry in freely moving rats. i.c.v. administered PGE2 (100 ng) induced comparable increases in body temperature in young and old Long-Evans rats. In the two groups, PGE2-induced fever was similar both in latency-to-peak fever and maximal fever response. These data, and the previous data on IL-1beta, demonstrate that the brains of old and young rats are similar with respect to fever generation in response to the i.c.v. administration of two classes of immunomodulators.