Conditional corticotropin-releasing hormone overexpression in the mouse forebrain enhances rapid eye movement sleep

Impaired sleep and enhanced stress hormone secretion are the hallmarks of stress-related disorders, including major depression. The central neuropeptide, corticotropin-releasing hormone (CRH), is a key hormone that regulates humoral and behavioral adaptation to stress. Its prolonged hypersecretion is believed to play a key role in the development and course of depressive symptoms, and is associated with sleep impairment. To investigate the specific effects of central CRH overexpression on sleep, we used conditional mouse mutants that overexpress CRH in the entire central nervous system (CRH-COE-Nes) or only in the forebrain, including limbic structures (CRH-COE-Cam). Compared with wild-type or control mice during baseline, both homozygous CRH-COE-Nes and -Cam mice showed constantly increased rapid eye movement (REM) sleep, whereas slightly suppressed non-REM sleep was detected only in CRH-COE-Nes mice during the light period. In response to 6-h sleep deprivation, elevated levels of REM sleep also became evident in heterozygous CRH-COE-Nes and -Cam mice during recovery, which was reversed by treatment with a CRH receptor type 1 (CRHR1) antagonist in heterozygous and homozygous CRH-COE-Nes mice. The peripheral stress hormone levels were not elevated at baseline, and even after sleep deprivation they were indistinguishable across genotypes. As the stress axis was not altered, sleep changes, in particular enhanced REM sleep, occurring in these models are most likely induced by the forebrain CRH through the activation of CRHR1. CRH hypersecretion in the forebrain seems to drive REM sleep, supporting the notion that enhanced REM sleep may serve as biomarker for clinical conditions associated with enhanced CRH secretion

Sleep disturbances in highly stress reactive mice: Modeling endophenotypes of major depression

<p>Abstract</p> <p>Background</p> <p>Neuronal mechanisms underlying affective disorders such as major depression (MD) are still poorly understood. By selectively breeding mice for high (HR), intermediate (IR), or low (LR) reactivity of the hypothalamic-pituitary-adrenocortical (HPA) axis, we recently established a new genetic animal model of extremes in stress reactivity (SR). Studies characterizing this SR mouse model on the behavioral, endocrine, and neurobiological levels revealed several similarities with key endophenotypes observed in MD patients. HR mice were shown to have changes in rhythmicity and sleep measures such as rapid eye movement sleep (REMS) and non-REM sleep (NREMS) as well as in slow wave activity, indicative of reduced sleep efficacy and increased REMS. In the present study we were interested in how far a detailed spectral analysis of several electroencephalogram (EEG) parameters, including relevant frequency bands, could reveal further alterations of sleep architecture in this animal model. Eight adult males of each of the three breeding lines were equipped with epidural EEG and intramuscular electromyogram (EMG) electrodes. After recovery, EEG and EMG recordings were performed for two days.</p> <p>Results</p> <p>Differences in the amount of REMS and wakefulness and in the number of transitions between vigilance states were found in HR mice, when compared with IR and LR animals. Increased frequencies of transitions from NREMS to REMS and from REMS to wakefulness in HR animals were robust across the light-dark cycle. Detailed statistical analyses of spectral EEG parameters showed that especially during NREMS the power of the theta (6-9 Hz), alpha (10-15 Hz) and eta (16-22.75 Hz) bands was significantly different between the three breeding lines. Well defined distributions of significant power differences could be assigned to different times during the light and the dark phase. Especially during NREMS, group differences were robust and could be continuously monitored across the light-dark cycle.</p> <p>Conclusions</p> <p>The HR mice, i.e. those animals that have a genetic predisposition to hyper-activating their HPA axis in response to stressors, showed disturbed patterns in sleep architecture, similar to what is known from depressed patients. Significant alterations in several frequency bands of the EEG, which also seem to at least partly mimic clinical observations, suggest the SR mouse lines as a promising animal model for basic research of mechanisms underlying sleep impairments in MD.</p

Cellular localization of human p53 expressed in the yeast Saccharomyces cerevisiae: effect of NLSI deletion

International audienceThe tumor suppressor p53 plays a central role in the regulation of cellular growth and apoptosis. In Saccharomyces cerevisiae, over-expression of the human wtp53 leads to growth inhibition and cell death on minimal medium. In the present work, we showed that deletion of the nuclear localization signal (NLSI) of p53 restores the yeast growth. In this heterologous context, the level of p53∆NLSI was low and the protein mainly located in the cytoplasm while the wtp53 was observed in both the cytoplasmic and nuclear compartments. Interestingly, the wtp53 protein was observed in the mitochondria, whereas the p53∆NLSI protein failed to localize in mitochondria. Moreover, mitochondrial morphology defect and release of cytochrome c in the cytosol were noticed only in the yeast strain expressing the wtp53. In conclusion, our results provide evidence that the human wtp53 is active in S. cerevisiae probably through dependent and independent transcriptional mechanisms leading to cell death. The deletion of the NLSI sequence decreases p53 nuclear translocation as well as its mitochondrial localization and consequently its effect on yeast growth

Aggressiveness, hypoalgesia and high blood pressure in mice lacking the adenosine A2a receptor.

Adenosine is released from metabolically active cells by facilitated diffusion, and is generated extracellularly by degradation of released ATP. It is a potent biological mediator that modulates the activity of numerous cell types, including various neuronal populations, platelets, neutrophils and mast cells, and smooth muscle cells in bronchi and vasculature. Most of these effects help to protect cells and tissues during stress conditions such as ischaemia. Adenosine mediates its effects through four receptor subtypes: the A1, A2a, A2b and A3 receptors. The A2a receptor (A2aR) is abundant in basal ganglia, vasculature and platelets, and stimulates adenylyl cyclase. It is a major target of caffeine, the most widely used psychoactive drug. Here we investigate the role of the A2a receptor by disrupting the gene in mice. We found that A2aR-knockout (A2aR-/-) mice were viable and bred normally. Their exploratory activity was reduced, whereas caffeine, which normally stimulates exploratory behaviour, became a depressant of exploratory activity. Knockout animals scored higher in anxiety tests, and male mice were much more aggressive towards intruders. The response of A2aR-/- mice to acute pain stimuli was slower. Blood pressure and heart rate were increased, as well as platelet aggregation. The specific A2a agonist CGS 21680 lost its biological activity in all systems tested.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

New records of rare species in the Mediterranean Sea (December 2022)

This Collective Article presents information on 20 taxa belonging to five (5) Phyla: Cnidaria (2), Mollusca (8), Arthropoda (4), Echinodermata (1) and Chordata (5) recorded from the Alboran Sea to the Levantine Sea. These new records were found in seven (7) different ecoregions as follows: Alboran Sea: new record of the rare football octopus Ocythoe tuberculata in the harbour of Algeciras (Spain); Western Mediterranean Sea: first record of the isopod Arcturinella deltensis in the Ligurian Sea, and the third in the whole Mediterranean Sea; third Mediterranean site for the Muricidae Coralliophila ahuiri along the Italian coasts (Alghe-ro); first and westernmost record of the goby Corcyrogobius liechtensteini from the Iberian Peninsula; new record of the sea slug Glaucus atlanticus from the coast of the Iberian Peninsula; first and easternmost record of Holothuria (Vaneyothuria) lentiginosa lentiginosa along the Italian coasts; Tunisian Plateau/Gulf of Sidra: seventh record of the oceanic squid Thysanoteuthis rhombus in Tunisia, and first for the Gulf of Gabes. Ionian Sea: second occurrence of the Atlantic tripletail Lobotes surinamensis in the Ionian Sea and first record from the Strait of Messina area; new record of the rare sea elephant Pterotrachea coronata from the Strait of Messina; Adriatic Sea: first record of a facies of football ascidian Diazona violacea in the South Adriatic Sea (Tremiti Island, Italy); two records of the sevengill shark Heptranchias perlo in Croatian waters after more than 70 years of absence of documented records in this area; first known occurrence of the nudibranch Jalonus hyalinus in Slovenian waters and also the first known occurrence of this species in the Adriatic Sea; first record of the nudibranch Okenia elegans in Slovenian waters; Aegean Sea: First record of the parasitic isopod Nerocila milesensis along Greek coasts (Crete island) as well as the second record world-wide; additional record of the brachyuran Paragalene longicrura collected from the Saronikos Gulf (Greece); first record of the siphonophore Rhizophysa filiformis in Greek waters as well as the second record of this species in the eastern Mediterranean basin; new record of the rare and protected angelshark Squatina aculeata along Turkish coasts; Levantine Sea: first record of the marine amphipod Caprella andreae in the Levantine Mediterranean shore of Israel, based on both morphological and molecular data; first occurrence of the cephalopod Tremoctopus violaceus along Turkish coasts, which confirms its presence in the north-eastern coasts of Turkey; record of a bloom of the thermophilic jellyfish Pelagia noctiluca in the north Levantine Sea