Anne Marita Milde

The effects of postnatal maternal separation on stress responsivity and experimentally induced colitis in adult rats

In this study, we investigated the effects of three neonatal conditions on adult corticosterone (CORT) levels, acoustic startle responses (ASRs), and vulnerability to colitis induced by dextran sulfate sodium (DSS) and how these early manipulations might interact with a brief stress exposure in adulthood on the same measures. Infant animals were subjected daily to either 180-min maternal separation [prolonged maternal separation (LMS)], 10-min maternal separation [brief maternal separation (BMS)], or nonhandling (NH) conditions during postnatal days 1-14. As adults, half of the animals were exposed to a series of 10 uncontrollable foot shocks. Animals were tested for CORT levels prior to and 10 days following shock/nonshock procedures before being tested for ASRs. Finally, all animals were exposed to 4% DSS in their drinking water for 6 days. LMS animals showed enhanced vulnerability to DSS-induced colitis when previously exposed to shock and enhanced stress reactivity responses as shown by elevated startle and CORT levels. Among the nonshocked animals, NH animals showed most colonic damage. Taken together, the results support previous findings suggesting that BMS has a protective effect on adult stress exposure. Additionally, BMS protects the animals from chemically induced colitis. The NH condition has clearly an effect on sensitizing mucosal response to DSS exposure.

Low‐dose oral ferrous fumarate aggravated intestinal inflammation in rats with dss‐induced colitis

Background: Oral ferrous iron therapy may reinforce intestinal inflammation. One possible mechanism is by catalyzing the production of reactive oxygen species. We studied the effects of low‐dose oral ferrous fumarate on intestinal inflammation and plasma redox status in dextran sulfate sodium (DSS)‐induced colitis in rats. Methods: Forty male Wistar rats were divided into 5 groups: no intervention, sham gavage (distilled water), ferrous fumarate, DSS, and ferrous fumarate + DSS. Ferrous fumarate was dissolved in distilled water (0.60 mg Fe2+/kg per day) and administered by gavage on days 1 to 14. All rats were fed a standard diet. Colitis was induced by 5% DSS in drinking water on days 8 to 14. Rats were killed on day 16. Histologic colitis scores, fecal granulocyte marker protein, plasma malondialdehyde, plasma antioxidant vitamins, and plasma aminothiols were measured. Results: DSS significantly increased histologic colitis scores (P < 0.001) and fecal granulocyte marker protein (P < 0.01). Ferrous fumarate further increased histologic colitis scores (P < 0.01) in DSS‐induced colitis. DSS + ferrous fumarate decreased plasma vitamin A compared with controls (P < 0.01). Otherwise, no changes were seen in plasma malondialdehyde, plasma antioxidant vitamins, or plasma aminothiols. Conclusion: Low‐dose oral ferrous iron enhanced intestinal inflammation in DSS‐induced colitis in rats.

Sleep disturbances in sexual abuse victims: A systematic review

An impressive body of research has investigated whether sexual abuse is associated with sleep disturbances. Across studies there are considerable differences in methods and results. The aim of this paper was to conduct the first systematic review of this area, as well as to clarify existing results and to provide guidelines for future research. We conducted searches in the electronic databases PsycINFO and PubMed up until October 2010 for studies on sleep disturbances in sexually abused samples. Thirty-two studies fulfilled the inclusion criteria (reported empirical data, included sexually abused subjects, employed some form of sleep measurement, English language and published in peer reviewed journals). Across the studies included, sleep disturbances were widespread and more prevalent in sexually abused subjects as compared to in non-abused samples. Symptoms reported more frequently by sexually abused samples included nightmare related distress, sleep paralysis, nightly awakenings, restless sleep, and tiredness. Results were divergent with regards to sleep onset difficulties, nightmare frequency, nocturnal activity, sleep efficiency, and concerning the proportion of each sample reporting sleep disturbances as such. Potential sources of these divergences are examined. Several methodological weaknesses were identified in the included studies. In order to overcome limitations, future researchers are advised to use standardized and objective measurements of sleep, follow-up or longitudinal designs, representative population samples, large sample sizes, adequate comparison groups, as well as comparison groups with other trauma experiences.

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.

A study of the effects of restraint stress on colitis induced by dextran sulphate sodium in singly housed rats.

The inflammatory bowel diseases (Crohn’s disease and ulcerative colitis) are multifactorial diseases. Clinical reports indicate that emotional stress may contribute to the onset, progression and remission of these diseases. Using an experimental animal model of ulcerative colitis, the effect of stress on the development of and recovery from symptoms, was studied prospectively. Singly housed rats received 4 percent dextran sulphate sodium orally until, fecal blood was detected, indicating the presence of colonic erosions. Tap water was then administered until there were no signs of fecal blood. Two hours of restraint stress were administered daily over four successive days, either prior to or after the induction of colitis. Latencies in days to symptom development and recovery were compared to an unstressed, group. Daily measures of fluid-intake, body-weight, and hemoglobulin in feces were made.ResultsRats exposed to restraint stress procedures prior to induction of colitis had shorter latencies to development of symptoms. There was no significant difference in latency to recovery. The amount of fluid-intake did not significantly differ between groups, nor did the groups differ in body-weight.ConclusionThere is an effect of stress on the latency to develop colitis induced by dextran sulphate sodium. This preliminary study suggests that the impact of stress may be one factor underlying the emergence of ulcerative colitis.

A comparison of Narrative Exposure Therapy and Prolonged Exposure therapy for PTSD

The purpose of this review was to compare and contrast Prolonged Exposure (PE) and Narrative Exposure Therapy (NET). We examined the treatment manuals to describe the theoretical foundation, treatment components, and procedures, including the type, manner, and focus of exposure techniques and recording methods used. We examined extant clinical trials to investigate the range of treatment formats reported, populations studied, and clinical outcome data. Our search resulted in 32 studies on PE and 15 studies on NET. Consistent with prior reviews of PTSD treatment, it is evident that PE has a solid evidence base and its current status as a first line treatment for the populations studied to this date is warranted. We argue that NET may have advantages in treating complex traumatization seen in asylum seekers and refugees, and for this population NET should be considered a recommended treatment. NET and PE have several commonalities, and it is recommended that studies of these treatments include a broader range of populations and trauma types to expand the current knowledge on the treatment of PTSD.

Long-term effects of footshock and social defeat on anxiety-like behaviours in rats: Relationships to pre-stressor plasma corticosterone concentration

We compared the consequences of two stressors, ‘unnatural’ inescapable footshocks (IFSs) and ‘natural’ social defeat (SD), on behaviours typically sensitive to stress [sucrose preference, open field (OF), elevated plus maze (EPM) and acoustic startle responses (ASRs)] and the association with pre-stressor plasma corticosterone concentration. After initial blood sampling, rats (n = 20 per group) were exposed to either 10 IFSs (1 mA intensity, 5 s duration each) or to 1 h SD (defeat by an aggressive resident male rat and further exposure but separated in a small cage) or to control procedures (handling). Rats were tested once for ASR (day 19), while the other behavioural tests were applied once weekly for 3 weeks. Both stress groups showed short-lasting lowered sucrose preference, and in the EPM they showed shorter total distance moved, shorter distance moved on open arms and less time on open arms compared to controls. In the OF test, IFS rats showed shorter total distance moved up to 2 weeks after stress. The SD group showed shorter total distance moved in the OF, which was only significant 2 weeks after stress. Low pre-stressor plasma corticosterone concentration was only associated with defecation (IFS rats) and latency to enter open arms in the EPM (all low corticosterone subgroups, n = 10 per subgroup). SD rats with high initial plasma corticosterone concentration showed enhanced ASR compared to the other subgroups with high initial plasma corticosterone concentration (n = 9 per subgroup). The results indicate that footshock and SD, while generally leading to an increase in anxiety behaviours, represent qualitatively different stressors.

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.

A salmon based diet protects mice from behavioural changes in the cuprizone model for demyelination

BACKGROUND & AIMS Although many patients with multiple sclerosis (MS) use special diets, the data available at present are insufficient to assess any potential benefit of diet modification. Cuprizone induced demyelination is a commonly used animal model for demyelination in the central nervous system. METHODS The present study was designed to analyse behaviour and activity due to demyelination in mice fed with 0.2% cuprizone on three different diets. The diets consisted of (1) salmon fillets rich in marine n-3 polyunsaturated fatty acids (PUFAs), (2) cod liver oil rich in marine n-3 PUFAs, or (3) a control diet containing soybean oil rich in n-6 PUFAs. After 5 weeks of continuous cuprizone treatment, animal activity was assessed with the elevated plus maze (EPM) test. After 6 weeks the brains were fixated in paraformaldehyde and stained with luxol fast blue (LFB). RESULTS There was significantly less demyelination in the salmon-cuprizone group than in the two other cuprizone-treatment groups (P<0.0005). The salmon-cuprizone mice had less weight loss (P<0.001) and showed more visits in both open and closed arms of the elevated plus maze than the other cuprizone-treated groups (P<0.0001). In addition they had more entries in the open arms than both the cod liver oil-cuprizone (P<0.02) and the soybean oil-cuprizone-treated mice (P<0.0001). CONCLUSIONS A diet containing salmon seems to protect against behavioural changes induced by demyelination in the cuprizone model, indicating that a fish diet could have a protective effect in demyelinating diseases.

Insomnia, Nightmare Frequency, and Nightmare Distress in Victims of Sexual Abuse: The Role of Perceived Social Support and Abuse Characteristics

In this study of victims of sexual abuse, the aim was to investigate the role of perceived social support and abuse characteristics in self-reported insomnia, nightmare frequency, and nightmare distress. Four hundred sixty Norwegian victims of sexual abuse completed a questionnaire assessing perceived social support, abuse characteristics, insomnia, nightmare frequency, and nightmare distress. Results show that higher levels of perceived social support were related to lower scores on all symptom outcome measures. Abuse involving oral, genital, or anal penetration was related to more insomnia symptoms. Longer duration of abuse and threatening conducted by the perpetrator were related to higher nightmare frequency, while threats and abuse involving penetration were related to higher degrees of distress associated with nightmares. In conclusion, the present study provides preliminary data indicating that perceived social support may affect the nature of sleep difficulties in sexual abuse victims. Also, more severe forms of sexual abuse are related to higher levels of sleep difficulties.