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Biomedical subjects

Reidun Ursin

Publications and source records attributed to Reidun Ursin.

7 recordsLinked to original sources

Chronic mild stress inhibits BDNF protein expression and CREB activation in the dentate gyrus but not in the hippocampus proper.

Chronic stress is linked to development of depression and may trigger neurobiological changes underlying the disease. Downregulation of the secretory peptide brain-derived neurotrophic factor (BDNF) and the transcriptional regulator calcium/cyclic-AMP responsive binding protein (CREB) have been implicated in stress and depression-related pathology in animal studies. When animals are exposed to the chronic mild stress (CMS) protocol, multiple depression-like symptoms are observed. Here we investigated the effect of CMS on BDNF protein expression and CREB activation in the dentate gyrus and hippocampus proper. Rats exposed for 5 weeks to repeated, unpredictable, mild stressors showed reduced BDNF expression and inhibited phosphorylation of CREB (Ser-133) in the dentate gyrus (-25.0%+/-3.5% and -29.7+/-7.3%, respectively), whereas no significant effects were observed in the hippocampus proper. CMS-treated rats consumed less sucrose compared to control rats, indicating a state of anhedonia. Moreover, phospho-CREB levels in the dentate gyrus were positively correlated with the animals' sucrose intake at the end of the CMS protocol. These results couple chronic mild stress to a downregulation of CREB activity and BDNF protein expression specifically within the dentate gyrus and support the possibility that the BDNF-CREB system plays an important role in the response to environmental challenges.

Animals↗

The effect of GABA(A) antagonist bicuculline on dorsal raphe nucleus and frontal cortex extracellular serotonin: a window on SWS and REM sleep modulation.

We investigated the effects of the perfusion of gamma-aminobutyric acid(A) antagonist bicuculline in the dorsal raphe nucleus, on brain 5-hydroxytryptamine level and on sleep. Perfusion of 25 and 50 microM bicuculline into the dorsal raphe nucleus dose-dependently increased dorsal raphe nucleus 5-hydroxytryptamine level during sleep and wakefulness. Frontal cortex 5-hydroxytryptamine level was not affected by either 25 or 50 microM perfusion. 25 microM bicuculline produced only minimal effects on sleep. 50 microM decreased rapid eye movement sleep, slow wave sleep 1 and 2 and increased waking. Sleep changes leveled out towards the end of the bicuculline perfusion despite serotonin levels were still elevated. This suggests that an adaptation mechanism may take place in order to counteract the high serotonergic output, producing uncoupling between serotonin level and behavioural state. The results support the notion that gamma-aminobutyric acid is a strong modulator of dorsal raphe nucleus serotonergic neurons, and that this modulation is important in the regulation of slow wave sleep, rapid eye movement sleep and waking.

Animals↗

Effects of chronic mild stress on sexual behavior, locomotor activity and consumption of sucrose and saccharine solutions.

Many symptoms of human depressive disorders are also observed in animals after exposure to unpredictable stressors. The chronic mild stress (CMS) paradigm was developed in order to better model the human situation by using chronic mild stressors over a longer period. It is claimed that the model induces anhedonia in the animals, a core symptom of depression in humans. Despite the fact that the CMS model has a high degree of face validity, there are a number of laboratories in which the establishment of the model is less reliably observed. We have examined behavior (sexual activity and open field activity) together with hedonic measures (sucrose and saccharine intake) after exposure to CMS. CMS decreased male sexual activity (e.g. reduced capability to ejaculate) and increased activity in an open field test. The hedonic measures showed diverging results after CMS in our laboratory. Sucrose consumption was reduced, while saccharine consumption did not show a comparable change. It is concluded that CMS induces comparable alterations to some depression-like symptoms in humans. Saccharine consumption is not a reliable indicator of the hedonic responsiveness to CMS.

Analysis of Variance↗

Seasonal variations in mood and behaviour associated with gender, annual income and education: the Hordaland Health Study.

OBJECTIVE: To explore the relationship between demographic factors and seasonal changes in mood and behaviour. METHOD: A health survey was conducted among 40-45 year old inhabitants in Hordaland County, Norway. The Global Seasonality Score, investigating seasonal symptoms, was given to 4299 men and 9983 women. Response rates among those receiving the questionnaire were 79.8% for men (n = 3432) and 81.2% for women (n = 8223). RESULTS: High seasonality was reported by 18.4% of men and 22.2% of women. Female gender, low educational level, high level of affective symptomatology and low household income correlated with high seasonality. Among men, being single was also a determinant factor for high seasonality. Reported seasonality also depended on which month the questionnaire was filled in. CONCLUSIONS: In this study, high seasonality was most prevalent among females, being single, having a low annual income and a low education level. The latter two findings are different from expectations which could be drawn from previous studies suggesting an opposite association.

Adult↗

Sleep duration, subjective sleep need, and sleep habits of 40- to 45-year-olds in the Hordaland Health Study.

STUDY OBJECTIVE: To report the distribution of various sleep parameters in a population-based study. DESIGN: Population-based cross-sectional study with self-administered questionnaires. SETTING: Conducted as part of the Hordaland Health Study '97-'99 in collaboration with the Norwegian National Health Screening Service. PARTICIPANTS: 8860 subjects, aged 40 to 45 years, answered the sleep questionnaire part of the study. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Reports on habitual bedtimes, rise times, subjective sleep need, and various sleep characteristics were used in this study. Mean (+/- SD) nocturnal sleep duration during weekdays in men was 6 hours 52 minutes (+/- 55 minutes); in women 7 hours 11 minutes (+/- 57 minutes). Mean subjective sleep need was 7 hours 16 minutes (+/- 52 minutes) in men; 7 hours 45 minutes (+/- 52 minutes) in women. Sleep duration was shorter in shift workers and longer in married subjects and in those living in rural areas. Subjective sleep need was higher in subjects reporting poor subjective health and in subjects living in rural areas. In total, these variables accounted for only around 3% of the variance in sleep duration and sleep need. Ten percent of the men and 12.2% of the women reported frequent insomnia. CONCLUSIONS: The wide distribution of sleep duration and subjective sleep need indicate large interindividual variations in these parameters. There were pronounced sex differences in these variables and in most of the sleep characteristics studied. Shift work, urban-rural living, marital status, and education in men were sources of significant, but small, variations in sleep duration.

Adult↗

Chronic mild stress affects sucrose intake and sleep in rats.

Depression in humans is associated with sleep abnormalities of three types: altered rapid eye movement (REM) sleep, fragmented sleep, and reduced delta sleep. In an animal model of depression, chronic exposure to mild stressors (CMS, e.g. periods of soiled cage, reversed light/dark cycle, grouped housing, food and/or water deprivation) causes behavioral and hormonal changes which, in humans, often are associated with depression. In the CMS model, a reduced sucrose intake has been defined as one of the core symptoms of depression, anhedonia, although this finding is not consistent among various laboratories. In the present study, we investigated if the CMS procedure, in our laboratory, would cause decreased sucrose intake and, also, give sleep changes similar to what is found in depressed patients. Exposure to CMS decreased sucrose intake in our rats. The largest effect was obtained after 2 weeks of the stress protocol. CMS rats spent more time in REM sleep and showed more fragmented sleep compared to their baseline recording, while there were no changes in the control rats. Increased sleep fragmentation in CMS rats was particularly evident by increased number of arousals, and increased REM sleep and slow-wave-sleep-1 (SWS-1) episodes. The duration of sleep stage episodes was decreased. The amount of slow-wave-sleep-2 (SWS-2) was not decreased, however SWS-2 in percent of total SWS was reduced. Correlation analysis showed that animals that had less consumption of sucrose spent more time in REM sleep and had increased number of REM sleep episodes. In this study, CMS appears to be a model of depression.

Animals↗

Serotonin and sleep.

For 50 years, serotonin has been in the centre of the search for the mechanisms and control of sleep. Serotonergic neurotransmission is related to the behavioural state of the animal and plays an important role in modulation of the behavioural state, by interacting with other brain areas modulating circadian rhythm, sleep and waking. Serotonergic activity may be accompanied by waking or sleep depending on the brain area and receptor type involved in the response, on the current behavioural state and on the concomitant agonism/antagonism of other neurotransmitter systems.

Brain↗