12 research outputs found
Nesfatin-1/NUCB2 as a Potential New Element of Sleep Regulation in Rats.
STUDY OBJECTIVES: Millions suffer from sleep disorders that often accompany severe illnesses such as major depression; a leading psychiatric disorder characterized by appetite and rapid eye movement sleep (REMS) abnormalities. Melanin-concentrating hormone (MCH) and nesfatin-1/NUCB2 (nesfatin) are strongly co - expressed in the hypothalamus and are involved both in food intake regulation and depression. Since MCH was recognized earlier as a hypnogenic factor, we analyzed the potential role of nesfatin on vigilance. DESIGN: We subjected rats to a 72 h-long REMS deprivation using the classic flower pot method, followed by a 3 h-long 'rebound sleep'. Nesfatin mRNA and protein expressions as well as neuronal activity (Fos) were measured by quantitative in situ hybridization technique, ELISA and immunohistochemistry, respectively, in 'deprived' and 'rebound' groups, relative to controls sacrificed at the same time. We also analyzed electroencephalogram of rats treated by intracerebroventricularly administered nesfatin-1, or saline. RESULTS: REMS deprivation downregulated the expression of nesfatin (mRNA and protein), however, enhanced REMS during 'rebound' reversed this to control levels. Additionally, increased transcriptional activity (Fos) was demonstrated in nesfatin neurons during 'rebound'. Centrally administered nesfatin-1 at light on reduced REMS and intermediate stage of sleep, while increased passive wake for several hours and also caused a short-term increase in light slow wave sleep. CONCLUSIONS: The data designate nesfatin as a potential new factor in sleep regulation, which fact can also be relevant in the better understanding of the role of nesfatin in the pathomechanism of depression
Chronic escitalopram treatment attenuated the accelerated rapid eye movement sleep transitions after selective rapid eye movement sleep deprivation: a model-based analysis using Markov chains
BackgroundShortened rapid eye movement (REM) sleep latency and increased REM sleep amount are presumed biological markers of depression. These sleep alterations are also observable in several animal models of depression as well as during the rebound sleep after selective REM sleep deprivation (RD). Furthermore, REM sleep fragmentation is typically associated with stress procedures and anxiety. The selective serotonin reuptake inhibitor (SSRI) antidepressants reduce REM sleep time and increase REM latency after acute dosing in normal condition and even during REM rebound following RD. However, their therapeutic outcome evolves only after weeks of treatment, and the effects of chronic treatment in REM-deprived animals have not been studied yet.ResultsChronic escitalopram- (10 mg/kg/day, osmotic minipump for 24 days) or vehicle-treated rats were subjected to a 3-day-long RD on day 21 using the flower pot procedure or kept in home cage. On day 24, fronto-parietal electroencephalogram, electromyogram and motility were recorded in the first 2 h of the passive phase. The observed sleep patterns were characterized applying standard sleep metrics, by modelling the transitions between sleep phases using Markov chains and by spectral analysis.Based on Markov chain analysis, chronic escitalopram treatment attenuated the REM sleep fragmentation [accelerated transition rates between REM and non-REM (NREM) stages, decreased REM sleep residence time between two transitions] during the rebound sleep. Additionally, the antidepressant avoided the frequent awakenings during the first 30 min of recovery period. The spectral analysis showed that the SSRI prevented the RD-caused elevation in theta (5 inverted question mark9 Hz) power during slow-wave sleep. Conversely, based on the aggregate sleep metrics, escitalopram had only moderate effects and it did not significantly attenuate the REM rebound after RD.ConclusionIn conclusion, chronic SSRI treatment is capable of reducing several effects on sleep which might be the consequence of the sub-chronic stress caused by the flower pot method. These data might support the antidepressant activity of SSRIs, and may allude that investigating the rebound period following the flower pot protocol could be useful to detect antidepressant drug response. Markov analysis is a suitable method to study the sleep pattern
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Differential adaptation of REM sleep latency, intermediate stage and theta power effects of escitalopram after chronic treatment.
The effects of the widely used selective serotonin reuptake
inhibitor (SSRI) antidepressants on sleep have been intensively
investigated. However, only a few animal studies examined the
effect of escitalopram, the more potent S-enantiomer of
citalopram, and conclusions of these studies on sleep
architecture are limited due to the experimental design. Here,
we investigate the acute (2 and 10 mg/kg, i.p. injected at the
beginning of the passive phase) or chronic (10 mg/kg/day for 21
days, by osmotic minipumps) effects of escitalopram on the sleep
and quantitative electroencephalogram (EEG) of Wistar rats. The
first 3 h of EEG recording was analyzed at the beginning of
passive phase, immediately after injections. The acutely
injected 2 and 10 mg/kg and the chronically administered 10
mg/kg/day escitalopram caused an approximately three, six and
twofold increases in rapid eye movement sleep (REMS) latency,
respectively. Acute 2-mg/kg escitalopram reduced REMS, but
increased intermediate stage of sleep (IS) while the 10 mg/kg
reduced both. We also observed some increase in light slow wave
sleep and passive wake parallel with a decrease in deep slow
wave sleep and theta power in both active wake and REMS after
acute dosing. Following chronic treatment, only the increase in
REMS latency remained significant compared to control animals.
In conclusion, adaptive changes in the effects of escitalopram,
which occur after 3 weeks of treatment, suggest desensitization
in the function of 5-HT(1A) and 5-HT(1B) receptors
Distribution of Secretin Receptors in the Rat Central Nervous System: an in situ Hybridization Study.
Secretin shows a wide distribution in the brain. Functional
significance of central secretin is stressed since it has been
associated with autism and schizophrenia. The presence of the
secretin receptor was previously demonstrated in the brain by
different methods. Neurons in the cerebellum, hypothalamic
paraventricular and supraoptic nuclei, and in the vascular organ
of lamina terminalis were shown to express secretin receptor
mRNA by using in situ hybridization with digoxigenin-labeled
probe. In this work, we used a very sensitive radioactive in
situ hybridization technique and systematically mapped the
expression of secretin receptor mRNA in the brain. The densest
labeling was observed in the nucleus of solitary tract and in
the laterodorsal thalamic nucleus, where decreasing number of
receptors was seen in the vascular organ of lamina terminalis,
and the lateral habenular complex, and then in the supraoptic
nucleus. Only a few scattered labeled cells were observed in the
median frontal gyrus, entorhinal cortex, hypothalamic
paraventricular nucleus, perifornical region, lateral
hypothalamic area, head of the caudate nucleus, spinal
trigeminal nucleus, and cerebellum. Secretin receptor mRNA
showed a far wider distribution than was known before,
suggesting a more significant functional relevance than thought
earlier
Exploring the role of neuropeptide S in the regulation of arousal: a functional anatomical study
Neuropeptide S (NPS) is a regulatory peptide expressed by limited number of neurons in the brainstem. The simultaneous anxiolytic and arousal-promoting effect of NPS suggests an involvement in mood control and vigilance, making the NPS-NPS receptor system an interesting potential drug target. Here we examined, in detail, the distribution of NPS-immunoreactive (IR) fiber arborizations in brain regions of rat known to be involved in the regulation of sleep and arousal. Such nerve terminals were frequently apposed to GABAergic/galaninergic neurons in the ventro-lateral preoptic area (VLPO) and to tyrosine hydroxylase-IR neurons in all hypothalamic/thalamic dopamine cell groups. Then we applied the single platform-on-water (mainly REM) sleep deprivation method to study the functional role of NPS in the regulation of arousal. Of the three pontine NPS cell clusters, the NPS transcript levels were increased only in the peri-coerulear group in sleep-deprived animals, but not in stress controls. The density of NPS-IR fibers was significantly decreased in the median preoptic nucleus-VLPO region after the sleep deprivation, while radioimmunoassay and mass spectrometry measurements showed a parallel increase of NPS in the anterior hypothalamus. The expression of the NPS receptor was, however, not altered in the VLPO-region. The present results suggest a selective activation of one of the three NPS-expressing neuron clusters as well as release of NPS in distinct forebrain regions after sleep deprivation. Taken together, our results emphasize a role of the peri-coerulear cluster in the modulation of arousal, and the importance of preoptic area for the action of NPS on arousal and sleep