Does a single exposure to social defeat render rats more vulnerable to chemically induced colitis than brief inescapable foot-shocks?

All mammals are to different degrees exposed to stressors being physical or social, which may affect health and well-being. Stressful and traumatic situations have direct effects on immune responses that may alter susceptibility to developing somatic illnesses. In animal research, different types of stressors have been investigated in studying the effect on bowel disorders, some stressors being more or less of environmental origin. We aimed, therefore, to explore whether a more natural stressor would differ from a stressor of more unnatural characteristics on dextran sulphate sodium (DSS) induced colitis in adult rats. Specifically, whether social stress within a single social defeat (SD) paradigm would be a more potent stressor than brief inescapable foot-shocks (IFS) in causing elevated faecal granulocyte marker protein (GMP), and crypt- and inflammation scores in colonic tissue. Three groups of male Wistar rats were used; socially defeated rats; inescapable foot-shock rats; and comparison rats. Main findings showed no difference between the groups on GMP levels. However, there was a significant difference on inflammation and crypt scores for the distal part of colon, detected through histology, where socially defeated rats were more susceptible. A single SD seems to be more adverse than inescapable foot-shock on DSS induced colitis, but further studies are recommended to validate a broader range of different outcomes comparing two such different rodent stress models.

Vitamin D Supplementation during Winter: Effects on Stress Resilience in a Randomized Control Trial.

Vitamin D status may be important for stress resilience. This study investigated the effects of vitamin D supplements during winter on biological markers of stress resilience such as psychophysiological activity, serotonin, and cortisol in a placebo-controlled, randomized clinical trial. Eighty-six participants were randomly assigned to the Intervention (vitamin D) or Control (placebo) groups. Before and after the intervention participants were exposed to an experimental stress procedure. Psychophysiological activity was measured during three main conditions: baseline, stress, and recovery. Fasting blood samples were taken in the morning and saliva samples were collected at seven different time points across 24 h. Prior to intervention both groups had normal/sufficient vitamin D levels. Both groups showed a normal pattern of psychophysiological responses to the experimental stress procedure (i.e., increased psychophysiological responses from resting baseline to stress-condition, and decreased psychophysiological responses from stress-condition to recovery; all p < 0.009). Post-intervention, the Intervention group showed increased vitamin D levels (p < 0.001) and normal psychophysiological responses to the experimental stress procedure (p < 0.001). Importantly, the Control group demonstrated a classic nadir in vitamin D status post-intervention (spring) (p < 0.001) and did not show normal psychophysiological responses. Thus, physiologically the Control group showed a sustained stress response. No significant effects of vitamin D were found on serotonin and cortisol.

A systematic review of studies utilizing hair glucocorticoids as a measure of stress suggests the marker is more appropriate for quantifying short-term stressors.

Quantitating glucocorticoids (GCs) in hairs is a popular method for assessing chronic stress in studies of humans and animals alike. The cause-and-effect relationship between stress and elevated GC levels in hairs, sampled weeks later, is however hard to prove. This systematic review evaluated the evidence supporting hair glucocorticoids (hGCs) as a biomarker of stress. Only a relatively small number of controlled studies employing hGC analyses have been published, and the quality of the evidence is compromised by unchecked sources of bias. Subjects exposed to stress mostly demonstrate elevated levels of hGCs, and these concentrations correlate significantly with GC concentrations in serum, saliva and feces. This supports hGCs as a biomarker of stress, but the dataset provided no evidence that hGCs are a marker of stress outside of the immediate past. Only in cases where the stressor persisted at the time of hair sampling could a clear link between stress and hGCs be established.

Comparison of commercial ELISA assays for quantification of corticosterone in serum.

Enzyme-linked immunosorbent assay (ELISA) kits are widely used to quantify corticosterone levels for the assessment of stress in laboratory animals. The aim of this experiment was simply to evaluate if four different and widely used commercial ELISA assays would yield the same or similar values of corticosterone in serum samples taken from laboratory rats after the mild stress of being held for sampling blood from the saphenous vein. Trunk blood was sampled from 32 male Wistar rats 30 minutes after this mild stress exposure and analysed with each of four commercial ELISA kits. Both the Arbor Assays and the DRG-4164 kits were significantly higher than the DRG-5186 and the Enzo kits. There were no significant differences between the DRG-5186 and Enzo kits. Overall the correlations between kits were high. In conclusion, the commercial ELISA kits tested in the present experiment yielded different values of total corticosterone in the same serum samples. The precision in determining true values of the corticosterone level is low for these commercial ELISA kits, although they may be used to determine relative differences within studies.

A Rodent Model of Night-Shift Work Induces Short-Term and Enduring Sleep and Electroencephalographic Disturbances.

Millions of people worldwide are working at times that overlap with the normal time for sleep. Sleep problems related to the work schedule may mediate the well-established relationship between shift work and increased risk for disease, occupational errors and accidents. Yet, our understanding of causality and the underlying mechanisms that explain this relationship is limited. We aimed to assess the consequences of night-shift work for sleep and to examine whether night-shift work-induced sleep disturbances may yield electrophysiological markers of impaired maintenance of the waking brain state. An experimental model developed in rats simulated a 4-day protocol of night-work in humans. Two groups of rats underwent 8-h sessions of enforced ambulation, either at the circadian time when the animal was physiologically primed for wakefulness (active-workers, mimicking day-shift) or for sleep (rest-workers, mimicking night-shift). The 4-day rest-work schedule induced a pronounced redistribution of sleep to the endogenous active phase. Rest-work also led to higher electroencephalogram (EEG) slow-wave (1-4 Hz) energy in quiet wakefulness during work-sessions, suggesting a degraded waking state. After the daily work-sessions, being in their endogenous active phase, rest-workers slept less and had higher gamma (80-90 Hz) activity during wake than active-workers. Finally, rest-work induced an enduring shift in the main sleep period and attenuated the accumulation of slow-wave energy during NREM sleep. A comparison of recovery data from 12:12 LD and constant dark conditions suggests that reduced time in NREM sleep throughout the recorded 7-day recovery phase induced by rest-work may be modulated by circadian factors. Our data in rats show that enforced night-work-like activity during the normal resting phase has pronounced acute and persistent effects on sleep and waking behavior. The study also underscores the potential importance of animal models for future studies on the health consequences of night-shift work and the mechanisms underlying increased risk for diseases.

Mild daily stressors in adulthood may counteract behavioural effects after constant presence of mother during early life.

This study investigated adult rat behaviour in three early life conditions, and how behaviour was affected after exposure to chronic mild stressors in later life. During postnatal days 2-14, male Wistar rats were exposed daily to either long or brief maternal separation, or were left undisturbed with their mothers (non-handled). As adults, non-handled and long maternally separated offspring demonstrated less object exploration than brief maternally separated offspring. Non-handled offspring also showed lower pre-pulse inhibition compared to both long and brief maternally separated offspring. Sucrose preference and open field behaviour as adults did not differ between the early life conditions. Exposure to four weeks of chronic mild stress in adulthood (mimicking daily hassles in humans) increased object exploration, increased pre-pulse inhibition and induced habituation of acoustic startle in non-handled offspring, similar to brief maternally separated offspring. Long maternally separated offspring exposed to chronic mild stress failed to show an increase in object exploration and enhanced pre-pulse inhibition, and did not show habituation of acoustic startle. In conclusion, different early life conditions have a different long-term impact on behaviour. Offspring from all three conditions differed from each other in terms of adult behaviour. Mild daily stressors in the adulthood counteracted the effects observed in the non-handled condition.

Cognitive functioning and cortisol profiles in first episode major depression.

Major Depressive Disorder (MDD) is often associated with high levels of stress and disturbances in the Hypothalamic Pituitary Adrenal (HPA) system, yielding high levels of cortisol, in addition to cognitive dysfunction. Previous studies have shown a relationship between cortisol profile and cognitive functioning in recurrent MDD in general. More specifically, the association between hypercortisolism and cognitive functioning, such as memory and Executive Functioning (EF), and also more recently cortisol suppression has been explored. However, no studies have investigated these relationships in patients diagnosed with first episode MDD. The aim of the present study was to examine the relationship between cortisol levels before and after the Dexamethasone suppression test (DST) and cognitive function in first episode MDD patients. Twenty-one patients meeting the DSM-IV criteria for a first episode of MDD diagnosis were included in the study. The control group was matched for age, gender and education level. Cortisol was measured in saliva collected with Salivette sampling devices. Saliva samples were collected 4 times during a 24 hours period over two consecutive days: at awakening, after 45 minutes, after 7 hours and at 11 pm. Dexamethasone (1.0 mg) was given orally on Day 1 at 11 pm. The neuropsychological test battery consisted of standardized tests measuring executive functioning (EF) and memory functioning. Cortisol levels did not differ significantly between patients and controls on Day 1, except for the last sample before Dexamethasone administration, where the control group showed higher levels. Both groups showed suppression after Dexamethasone. On Day 2 there was a significant difference between groups at the third sample, showing a significantly lower level in the control group, suggesting that the controls have a more effective suppression profile than the patients. There were no significant correlations between cortisol levels before or after Dexamethasone and cognitive measures. The results indicate impairment on HPA-axis functioning in first episode MDD patients, with less suppression functioning compared to healthy controls, but no relationship between cortisol profile and cognitive functioning in EF or Memory.

Maternal Deprivation of Lewis Rat Pups Increases the Severity of Experi-mental Periodontitis in Adulthood.

BACKGROUND AND OBJECTIVE: Early life adverse events may influence susceptibility/resistance to chronic inflammatory diseases later in life by permanently dysregulating brain-controlled immune-regulatory systems. We have investigated the impact of infant-mother separation during early postnatal life on the severity of experimental periodontitis, as well as systemic stress and immune responses, in adulthood. MATERIAL AND METHODS: Pups of periodontitis resistant Lewis rats were separated from their mothers for 3 h daily during postnatal days 2-14 (termed maternal deprivation; MD), separated for 15 min daily during the same time period (termed handling; HD), or left undisturbed. As adults, their behaviour was tested in a novel stressful situation, and ligature-induced periodontitis applied for 21 days. Two h before sacrifice all rats were exposed to a gram-negative bacterial lipopolysaccharide (LPS) challenge to induce a robust immune and stress response. RESULTS: Compared to undisturbed controls, MD rats developed significantly more periodontal bone loss as adults, whereas HD rats showed a tendency to less disease. MD and HD rats exhibited depression-like behaviour in a novel open field test, while MD rats showed higher glucocorticoid receptor (Gr) expression in the hippocampus, and HD rats had altered methylation of genes involved in the expression of hippocampal Gr. LPS provoked a significantly lower increase in circulating levels of the cytokine TGF-1ß in MD and HD rats, but there were no significant differences in levels of the stress hormone corticosterone. CONCLUSION: Stressful environmental exposures in very early life may alter immune responses in a manner that influences susceptibility/resistance to periodontitis.

Effects of social defeat on sleep and behaviour: importance of the confrontational behaviour.

We studied the short- and long-term effects of a double social defeat (SD) on sleep parameters, EEG power, behaviour in the open field emergence test, corticosterone responsiveness, and acoustic startle responses. Pre-stress levels of corticosterone were assessed before all rats were surgically implanted with telemetric transmitters for sleep recording, and allowed 3weeks of recovery. Rats in the SD group (n=10) were exposed to 1hour SD on two consecutive days, while control rats (n=10) were left undisturbed. Telemetric sleep recordings were performed before SD (day -1), day 1 post SD, and once weekly for 3weeks thereafter. The open field emergence test was performed on day 9 and weekly for 2weeks thereafter. Blood samples for measures of corticosterone responsiveness were drawn after the last emergence test (day 23). Acoustic startle responses were tested on day 24 post SD. Overall, SD rats as a group were not affected by the social conflict. Effects of SD seemed, however, to vary according to the behaviours that the intruder displayed during the social confrontation with the resident. Compared to those SD rats showing quick submission (SDS, n=5), SD rats fighting the resident during one or both SD confrontations before defeat (SDF, n=5) showed more fragmented slow wave sleep, both in SWS1 and SWS2. They also showed longer latency to leave the start box and spent less time in the open field arena compared to SDS rats. In the startle test, SDF rats failed to show response decrement at the lowest sound level. Our results indicate that how animals behave during a social confrontation is more important than exposure to the SD procedure itself, and that rapid submission during a social confrontation might be more adaptive than fighting back.

Hypothermia after chronic mild stress exposure in rats with a history of postnatal maternal separations.

The circadian system develops and changes in a gradual and programmed process over the lifespan. Early in life, maternal care represents an important zeitgeber and thus contributes to the development of circadian rhythmicity. Exposure to early life stress may affect circadian processes and induce a latent circadian disturbance evident after exposure to later life stress. Disturbance of the normal regulation of circadian rhythmicity is surmised to be an etiological factor in depression. We used postnatal maternal separation in rats to investigate how the early life environment might modify the circadian response to later life unpredictable and chronic stress. During postnatal days 2-14, male Wistar rats (n = 8 per group) were daily separated from their mothers for a period of either 180 min (long maternal separation; LMS) or 10 min (brief maternal separation; BMS). In adulthood, rats were exposed to chronic mild stress (CMS) for 4 weeks. Body temperature, locomotor activity and heart rate were measured and compared before and after CMS exposure. LMS offspring showed a delayed body temperature acrophase compared to BMS offspring. Otherwise, adult LMS and BMS offspring demonstrated similar diurnal rhythms of body temperature, locomotor activity and heart rate. Exposure to CMS provoked a stronger and longer lasting hypothermia in LMS rats than in BMS rats. The thermoregulatory response appears to be moderated by maternal care following reunion, an observation made in the LMS group only. The results show that early life stress (LMS) in an early developmental stage induced a thermoregulatory disturbance evident upon exposure to unpredictable adult life stressors.

Early and later life stress alter brain activity and sleep in rats.

Exposure to early life stress may profoundly influence the developing brain in lasting ways. Neuropsychiatric disorders associated with early life adversity may involve neural changes reflected in EEG power as a measure of brain activity and disturbed sleep. The main aim of the present study was for the first time to characterize possible changes in adult EEG power after postnatal maternal separation in rats. Furthermore, in the same animals, we investigated how EEG power and sleep architecture were affected after exposure to a chronic mild stress protocol. During postnatal day 2-14 male rats were exposed to either long maternal separation (180 min) or brief maternal separation (10 min). Long maternally separated offspring showed a sleep-wake nonspecific reduction in adult EEG power at the frontal EEG derivation compared to the brief maternally separated group. The quality of slow wave sleep differed as the long maternally separated group showed lower delta power in the frontal-frontal EEG and a slower reduction of the sleep pressure. Exposure to chronic mild stress led to a lower EEG power in both groups. Chronic exposure to mild stressors affected sleep differently in the two groups of maternal separation. Long maternally separated offspring showed more total sleep time, more episodes of rapid eye movement sleep and higher percentage of non-rapid eye movement episodes ending in rapid eye movement sleep compared to brief maternal separation. Chronic stress affected similarly other sleep parameters and flattened the sleep homeostasis curves in all offspring. The results confirm that early environmental conditions modulate the brain functioning in a long-lasting way.

The availability and mobility of arsenic and antimony in an acid sulfate soil pasture system.

The Macleay floodplain on the north coast of New South Wales, Australia, has surface soil concentrations of up to 40 mg kg(-1) arsenic (As) and antimony (Sb), due to historical mining practices in the upper catchment. The floodplain also contains areas of active and potential acid sulfate soils (ASS). Some of these areas are purposely re-flooded to halt oxidation processes, but the effect of this management on the metalloid mobility and phytoavailability of the metalloids present is unknown. This study investigated the changes to soil solution As and Sb, associations of metalloids with soil solid phases, and uptake into two common pasture species following 20 weeks of flooding in a controlled environment. The effect of an ASS subsoil was also investigated. The soil solution concentration and availability of the metalloids was in some instances higher in the floodplain soils than would generally be expected in soils with comparable contamination. There appeared to be few changes to soil solution concentrations or phase associations with flooding in this short term study, due to the high acid buffering and poise of the investigated soils. A strong relationship was found between the relative uptake of Sb into pastures and the oxalate extractable Fe in the soil, which was taken as a proxy for non-crystalline iron (Fe) hydroxides. This relationship was dependent on flooding and was absent for As. Further targeted investigations into metalloid speciation kinetics and the stability of soil solid phases with flooding management are recommended.

Restoring psychology's role in peptic ulcer.

This paper reviews the history of the transition from the belief that gastrointestinal ulcers are caused primarily by psychological factors to the current state of belief that they are caused primarily by infection and argues that neither is fully accurate. We argue that psychological factors play a significant role as predisposing to vulnerability, modulating of precipitation, and sustaining of gastric ulceration. We review data that challenge the assumption of a simple infectious disease model and adduce recent preclinical data that confirm the predisposing, modulatory, and sustaining roles for psychological factors. We note that others, too, are now challenging the adequacy of the contemporary simple bacterial infection model. We hope to replace the competition between psychology and medicine with cooperation in understanding and treating patients suffering gastric ulceration and ulcer.

Rate of change in physical fitness and quality of life and depression following exercise training in patients with congestive heart failure.

Exercise training appears to improve peak oxygen consumption (VO(2) ) and quality of life (QOL) in heart failure patients, although disease etiology, patient demographics and medication may alter the rate of adaptation. The authors sought to identify rate of change from baseline in fitness, QOL, and depression following exercise training in a cohort of patients with congestive heart failure. Thirty male systolic heart failure patients (aged 63.8±8.3 years, baseline peak VO(2) 12.2±4.8 mL/kg/min, left ventricular ejection fraction 28.2±9.4%, New York Heart Association class II/II 22/8) undertook 52 weeks of exercise training, 16 weeks as an outpatient and a further 36 weeks of home exercise. Peak VO(2) and QOL was measured using the Minnesota Living With Heart Failure (MLWHF) questionnaire and depression using the Hare-Davis scale. The authors analyzed the rate of change in peak VO(2) and MLWHF after grouping patients according to clinical, demographic, and pharmacologic characteristics. Peak VO(2) measurements varied over time, with no effect of disease pathology or ß-blocker on peak VO(2) . The rate of change in physical MLWHF score was significantly greater (improved) during 0 to 16 weeks in patients with dilated pathology, but was not significantly affected by ß-blocker use or age. The exercise training venue and supervision, or lack thereof, is the major determinant of adaptation to the intervention in heart failure patients, although age, ß-adrenergic medication, and heart failure etiology also explain some of the variation in adaptive responses observed.

Maternal depression and infant daytime cortisol.

The effect of maternal depressive disorder on infant daytime cortisol production was studied in three groups of infants; one group with mothers with comorbid depression and anxiety (n = 19), a second group with mothers with depression only (n = 7), and a third group with non-depressed mothers (n = 24). The infants' cortisol production pattern was measured when they were 6, 12, and 18 months old in combination with repeated measures of parenting stress and depression symptoms. Multilevel modeling analyses showed that infants of mothers with comorbid depression and anxiety had relatively higher cortisol production from morning to bedtime and higher bedtime values as compared to infants of non-depressed mothers and infants of depressed only mothers when they were 6 and 12 months old, but not when 18 months old. The results were interpreted in light of possible changes in the infants' stress regulatory capacities or changes in maternal coping strategies at infant age 18 months.

Cognitive functioning and cortisol suppression in recurrent major depression.

Major Depressive Disorder (MDD) is often associated with high levels of stress and disturbances in the hypothalamic-pituitary-adrenal (HPA) system, yielding high levels of cortisol in addition to cognitive dysfunction. The aim of the present study was to examine the relation between cortisol levels after the dexamethasone suppression test and cognitive function in recurrent unipolar MDD patients. Twenty-four patients meeting the Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.) criteria for a recurrent MDD diagnosis were included in the study. The control group was matched for age, sex, and education level. Cortisol was measured in saliva collected with Salivette sampling devices. Saliva samples were collected four times during a 24-hr period over two consecutive days: at awakening, after 45 min, after 7 hr, and at 11:00 p.m. One milligram of dexamethasone was given on Day 1 at 11:00 p.m. The neuropsychological test battery consisted of standardized tests measuring cognitive functioning within verbal and visual memory, as well as executive functioning. Cortisol levels did not differ between patients and controls on Day 1. Cortisol levels in patients were higher than in controls at awakening on Day 2 (D2S1), after dexamethasone administration the previous evening. All significant correlations between cognitive measures and cortisol at D2S1 were negative, indicating that low suppression after intake of dexamethasone is related to poor cognitive functioning. Significant relations were found in three of the cognitive tests measuring verbal memory, semantic fluency, and inhibition. The present findings indicate that dysregulation of the HPA-axis is related to poor verbal memory functioning. There was no firm evidence that abnormal cortisol levels were associated with inhibition difficulties.

Post-transcriptional effects and interactions between chronic mild stress and acute sleep deprivation: regulation of translation factor and cytoplasmic polyadenylation element-binding protein phosphorylation.

Stress and restricted or disrupted sleep trigger adaptive responses in the brain at the level of gene transcription. We investigated the possible impact of chronic mild stress (CMS), acute sleep deprivation, and a combination of these in male rats on post-transcriptional mechanisms important for cognitive function and synaptic plasticity. Relationships between sleep architecture and translational regulators were also assessed. After four weeks of CMS, phosphorylation of two key translation factors, eukaryotic initiation factor 4E (eIF4E) and elongation factor 2 (eEF2), was enhanced in the prefrontal cortex, but unchanged in the hippocampus and dentate gyrus. Sleep deprivation decreased phosphorylated eIF4E in the dentate gyrus. In contrast, eEF2 phosphorylation was elevated in all brain regions after sleep deprivation. Thus, CMS and sleep deprivation, when given alone, have distinct region-specific effects. Furthermore, the combined treatment revealed striking interactions with eEF2 phosphorylation in which sleep deprivation counteracts the effect of CMS cortically and CMS modulates the effects of sleep deprivation in the hippocampus proper. Although CMS exposure alone had no effect in the hippocampus, it inhibited the sleep deprivation-induced eIF4E phosphorylation, while inducing phosphorylation of a major regulatory RNA-binding protein, cytoplasmic polyadenylation element-binding protein (CPEB) in the combined treatment. CMS had no effect on plasma corticosterone, but led to disruption of sleep. Sleep quality and sleep quantity in non-stressed animals showed predictive changes in eIF4E and eEF2 phosphorylation cortically. Prior exposure to CMS abolishes this relationship. We conclude that CMS and acute sleep deprivation have interactive and brain region-specific effects on translational regulators of relevance to mechanisms of stress responsiveness and sleep homeostasis.

Heart rate variability and cortisol responses during attentional and working memory tasks in naval cadets.

The aim of the paper was to study the relationship between heart rate variability (HRV) and cortisol release during cognitive challenging tasks. Forty-nine male naval cadets from the Royal Norwegian Naval Academy were administered computerised versions of attentional and working memory tests. The results from this study support the hypothesis of a negative correlation between HRV and cortisol secretion during cognitive tasks. Confirmation of the hypothesis with the low HRV group scoring higher on cortisol only during performance of cognitive tasks and recovery was also found. Furthermore, a replication of the previous findings of a negative association between cortisol levels and performance were supported when using uncorrected comparisons. None of the correlations survived Bonferonin corrections. The findings are discussed in relation to factors increasing HRV, thus improving tolerance to cognitive stress in onboard environments.

Higher levels of fatigue are associated with higher CRP levels in disease-free breast cancer survivors.

OBJECTIVE: To investigate the associations between level of fatigue and various potential inflammatory biomarkers for fatigue after multivariate adjustments for possible confounders in a sample of 299 disease-free survivors of breast cancer (BCSs) at a mean of 4 years post diagnosis. METHODS: Medical record data were used for cancer-related information, and a follow-up mailed survey collected data on fatigue, depression, anxiety and insomnia symptoms as well as information on demographics, physical health, medication and lifestyle. Blood samples drawn at an outpatient examination were analyzed for leukocyte count, high sensitivity C-reactive Protein (CRP), interleukin 1 receptor antagonist (IL-1ra), interleukin-6 (IL-6), soluble tumor necrosis factor receptor type 1 (sTNF-R1) and neopterin. RESULTS: Fatigue levels were significantly and positively associated with hsCRP (p<.001) and leukocyte count (p=.018), but not with levels of IL-1ra, IL-6, sTNF-R1 or neopterin in unadjusted analyses. Only hsCRP remained significantly associated with fatigue levels in the fully adjusted models (p=.020). Depression and self-rated health also remained independently associated with fatigue; however these variables were not significantly associated with hsCRP in multivariate analyses. CONCLUSION: In general, and after adjustment for potential confounders, our hypotheses of positive associations between fatigue and several inflammatory markers were not confirmed. However, a small but independent association between level of fatigue and hsCRP was observed and supports the hypothesis that low-grade inflammation could play a role in the pathogenesis of fatigue in BCSs.

Emotional stress and orthodontic tooth movement: effects on apical root resorption, tooth movement, and dental tissue expression of interleukin-1 alpha and calcitonin gene-related peptide immunoreactive nerve fibres in rats.

The aim of the study was to investigate the effect of emotional stress on apical root resorption (ARR) and tooth displacement during orthodontic tooth movement in rats. A further area of interest was to evaluate if the expression of interleukin-1 alpha (IL-1alpha) as well as the density and distribution of peptidergic nerve fibres immunoreactive to calcitonin gene-related peptide (CGRP) in the periodontal ligament (PDL) are associated with possible stress-induced changes in root resorption and tooth movement. A total of 52 male Wistar rats, aged 6 weeks, were divided in three experimental and one control group (n = 4). Group 1 had orthodontic tooth movement and received foot shocks (OTMS; n = 16), group 2 had orthodontic tooth movement but received no foot shocks (OTMNS; n = 16), and group 3 had no orthodontic tooth movement and received foot shocks (NOTMS; n = 16). Each group was further divided into four subgroups (n = 4), corresponding to the period of the experiment, i.e. 3, 7, 13, and 21 days. At the end of each experimental period, the blood samples were taken, the animals were sacrificed, and the jaws excised, deminerialized, and processed for immunocytochemistry. One-way analysis of variance was used to detect inter-group differences for all investigated variables. CGRP immunopositive nerve fibres were evaluated qualitatively. All the experimental groups demonstrated higher corticosterone levels than the control group, suggesting a stress-induced experience by orthodontic treatment per se. The OTMS group had the least amount of cellular cementum throughout the experimental periods and showed significant reduction in tooth displacement, especially at 3 and 7 days. No obvious changes were observed in the dental tissue expression of IL-1alpha and CGRP immunoreactive nerve fibres between the stressed and non-stressed orthodontically treated groups.