mRNA expression in mouse hypothalamus and basal forebrain during influenza infection: a novel model for sleep regulation

2006 ◽  
Vol 24 (3) ◽  
pp. 225-234 ◽  
Author(s):  
Ming Ding ◽  
Linda A. Toth

After influenza infection, C57BL/6J mice develop increased slow-wave sleep (SWS) during the dark phase of the day-night cycle, whereas BALB/cByJ mice develop decreased SWS during the light phase. A previous analysis of CXB recombinant inbred mice revealed a quantitative trait locus (QTL) designated Srilp (sleep response to influenza, light phase) that was related to expression of the BALB/cByJ sleep phenotype. Srilp was localized to the 10- to 12-cM region of mouse Chr 6 between D6Mit74 and D6Mit188. Temt (thioether S-methyltransferase), which is located at region B3 of Chr 6, is a potential candidate gene for Srilp. We evaluated the expression of Temt and other Srilp candidate genes in hypothalamus and basal forebrain of uninfected and influenza-infected C57BL/6J and BALB/cByJ mice. We report here that Temt expression varies significantly with respect to mouse strain, health status, brain region, and day-night phase. C57BL/6J mice show day-night variation in Temt expression in hypothalamus, but BALB/cByJ mice do not. Temt expression in basal forebrain is much higher in C57BL/6J mice than in BALB/cByJ mice. During influenza infection, both C57BL/6J and BALB/cByJ mice show reduced Temt mRNA in basal forebrain at 30 h postinoculation, but expression remains much lower in the BALB/cByJ strain. In contrast, prostaglandin-d-synthase ( Ptgds) and lipocalin 2 ( Lcn2) mRNA increase in basal forebrain of both strains after influenza infection. Administration of the TEMT inhibitor sinefungin reduces sleep in uninfected BALB/cByJ mice and attenuates influenza-induced sleep enhancement in C57BL/6J mice. These data suggest that strain- and infection-related alterations in sleep may be influenced by Temt expression and perhaps by subsequent effects on prostaglandin metabolism.

2001 ◽  
Vol 281 (1) ◽  
pp. R170-R175 ◽  
Author(s):  
Alfredo Manfridi ◽  
Dario Brambilla ◽  
Mauro Mancia

There is evidence that GABA plays a major role in sleep regulation. GABAA receptor agonists and different compounds interacting with the GABAA receptor complex, such as barbiturates and benzodiazepines, can interfere with the sleep/wake cycle. On the other hand, there is very little information about the possible role of GABAB receptors in sleep modulation. The nucleus basalis of Meynert (NBM), a cholinergic area in the basal forebrain, plays a pivotal role in the modulation of sleep and wakefulness, and both GABAA and GABABreceptors have been described within the NBM. This study used unilateral infusions in the NBM to determine the effects of 3-hydroxy-5-aminomethylisoxazole hydrobromide (muscimol hydrobromide, a GABAA receptor subtype agonist) and β-(aminomethyl)-4-chlorobenzenepropanoic acid (baclofen, a GABAB receptor subtype agonist) on sleep parameters in freely moving rats by means of polygraphic recordings. Muscimol (0.5 nmol) and baclofen (0.7 nmol) induced an increase in slow-wave sleep and an inhibition of wakefulness. Muscimol, but not baclofen, also caused a decrease in desynchronized sleep parameters. The results reported here indicate that 1) the NBM activation of both GABAA and GABAB receptors influences the sleep/wake cycle, and 2) GABAA but not GABAB receptors are important for desynchronized sleep modulation, suggesting that the two GABAergic receptors play different roles in sleep modulation.


2001 ◽  
Vol 280 (6) ◽  
pp. R1806-R1814 ◽  
Author(s):  
Linda A. Toth ◽  
Mark R. Opp

Interleukin (IL)-1 and tumor necrosis factor (TNF) promote slow-wave sleep (SWS), whereas IL-10 inhibits the synthesis of IL-1 and TNF and promotes waking. We evaluated the impact of endogenous IL-10 on sleep-wake behavior by studying mice that lack a functional IL-10 gene. Under baseline conditions, C57BL/6-IL-10 knockout (KO) mice spent more time in SWS during the dark phase of the light-dark cycle than did genetically intact C57BL/6 mice. The two strains of mice showed generally comparable responses to treatment with IL-1, IL-10, or influenza virus, but differed in their responses to lipopolysaccharide (LPS). In IL-10 KO mice, LPS induced an initial transient increase and a subsequent prolonged decrease in SWS, as well as profound hypothermia. These responses were not observed in LPS-treated C57BL/6 mice. These data demonstrate that in the absence of endogenous IL-10, spontaneous SWS is increased and the impact of LPS on vigilance states is altered. Collectively, these observations support a role for IL-10 in sleep regulation and provide further evidence for the involvement of cytokines in the regulation of sleep.


2000 ◽  
Vol 279 (6) ◽  
pp. R2173-R2178 ◽  
Author(s):  
Didier Chollet ◽  
Paul Franken ◽  
Yvette Raffin ◽  
Alain Malafosse ◽  
Jean Widmer ◽  
...  

A strong genetic component in the regulation of blood magnesium (Mg) levels has been demonstrated. The regulation and distribution of brain Mg levels, however, have never been assessed. Herein we report on the genetic variation of peripheral and central Mg levels in six inbred strains of mice. In addition, the possible involvement of Mg in sleep regulation was assessed by establishing correlations between Mg and sleep parameters obtained before and after a 6-h sleep deprivation. Although genotype strongly determined blood Mg levels, it did not affect brain Mg, suggesting that central and peripheral Mg are regulated differently. Central Mg displayed a highly structure-specific distribution with frontal cortex having the highest and brain stem the lowest values. Whereas for the amount and distribution of baseline sleep only marginal correlations with Mg were found, Mg contents in four of nine brain structures were highly positively correlated with the length of slow-wave sleep episodes during recovery. This relationship suggests that higher levels of Mg in specific brain sites promote sleep quality as part of a recovery process.


2019 ◽  
Vol 20 (10) ◽  
pp. 2452 ◽  
Author(s):  
Martha López-Canul ◽  
Seung Hyun Min ◽  
Luca Posa ◽  
Danilo De Gregorio ◽  
Annalida Bedini ◽  
...  

Melatonin (MLT) is a neurohormone that regulates many physiological functions including sleep, pain, thermoregulation, and circadian rhythms. MLT acts mainly through two G-protein-coupled receptors named MT1 and MT2, but also through an MLT type-3 receptor (MT3). However, the role of MLT receptor subtypes in thermoregulation is still unknown. We have thus investigated the effects of selective and non-selective MLT receptor agonists/antagonists on body temperature (Tb) in rats across the 12/12-h light–dark cycle. Rectal temperature was measured every 15 min from 4:00 a.m. to 9:30 a.m. and from 4:00 p.m. to 9:30 p.m., following subcutaneous injection of each compound at either 5:00 a.m. or 5:00 p.m. MLT (40 mg/kg) had no effect when injected at 5 a.m., whereas it decreased Tb during the light phase only when injected at 5:00 p.m. This effect was blocked by the selective MT2 receptor antagonist 4P-PDOT and the non-selective MT1/MT2 receptor antagonist, luzindole, but not by the α1/MT3 receptors antagonist prazosin. However, unlike MLT, neither the selective MT1 receptor partial agonist UCM871 (14 mg/kg) nor the selective MT2 partial agonist UCM924 (40 mg/kg) altered Tb during the light phase. In contrast, UCM871 injected at 5:00 p.m. increased Tb at the beginning of the dark phase, whereas UCM924 injected at 5:00 a.m. decreased Tb at the end of the dark phase. These effects were blocked by luzindole and 4P-PDOT, respectively. The MT3 receptor agonist GR135531 (10 mg/kg) did not affect Tb. These data suggest that the simultaneous activation of both MT1 and MT2 receptors is necessary to regulate Tb during the light phase, whereas in a complex but yet unknown manner, they regulate Tb differently during the dark phase. Overall, MT1 and MT2 receptors display complementary but also distinct roles in modulating circadian fluctuations of Tb.


1970 ◽  
Vol 48 (6) ◽  
pp. 1425-1427 ◽  
Author(s):  
John E. Byrne

Intraperitoneal injections administered for 3 consecutive days to juvenile sockeye salmon resulted in selective activity responses to either the light or the dark phase of the photoperiodic cycle. Serotonin increased locomotor activity only during the dark phase, while melatonin decreased locomotor activity only during the light phase.


Processes ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 2011
Author(s):  
David Ewusi-Mensah ◽  
Jingyu Huang ◽  
Laura Katherin Chaparro ◽  
Pau Rodenas ◽  
Marina Ramírez-Moreno ◽  
...  

Algae-assisted microbial desalination cells represent a sustainable technology for low-energy fresh water production in which microalgae culture is integrated into the system to enhance oxygen reduction reaction in the cathode chamber. However, the water production (desalination rate) is low compared to conventional technologies (i.e., reverse osmosis and/or electrodialysis), as biocathodes provide low current generation to sustain the desalination process. In this sense, more research efforts on this topic are necessary to address this bottleneck. Thus, this study provides analysis, from the electrochemical point of view, on the cathode performance of an algae-assisted microbial desalination cell (MDC) using Chlorella vulgaris. Firstly, the system was run with a pure culture of Chlorella vulgaris suspension in the cathode under conditions of an abiotic anode to assess the cathodic behavior (i.e., cathode polarization curves in light-dark conditions and oxygen depletion). Secondly, Geobacter sulfurreducens was inoculated in the anode compartment of the MDC, and the desalination cycle was carried out. The results showed that microalgae could generate an average of 9–11.5 mg/L of dissolved oxygen during the light phase, providing enough dissolved oxygen to drive the migration of ions (i.e., desalination) in the MDC system. Moreover, during the dark phase, a residual concentration of oxygen (ca. 5.5–8 mg/L) was measured, indicating that oxygen was not wholly depleted under our experimental conditions. Interestingly, the oxygen concentration was restored (after complete depletion of dissolved oxygen by flushing with N2) as soon as microalgae were exposed to the light phase again. After a 31 h desalination cycle, the cell generated a current density of 0.12 mA/cm2 at an efficiency of 60.15%, 77.37% salt was removed at a nominal desalination rate of 0.63 L/m2/h, coulombic efficiency was 9%, and 0.11 kWh/m3 of electric power was generated. The microalgae-assisted biocathode has an advantage over the air diffusion and bubbling as it can self-sustain a steady and higher concentration of oxygen, cost-effectively regenerate or recover from loss and sustainably retain the system’s performance under naturally occurring conditions. Thus, our study provides insights into implementing the algae-assisted cathode for sustainable desalination using MDC technology and subsequent optimization.


2021 ◽  
Vol 13 ◽  
Author(s):  
Felipe P. Fiuza ◽  
José Pablo G. Queiroz ◽  
Antônio Carlos Q. Aquino ◽  
Diego A. Câmara ◽  
Luiz Eduardo M. Brandão ◽  
...  

Aging affects the overall physiology, including the image-forming and non-image forming visual systems. Among the components of the latter, the thalamic retinorecipient inter-geniculate leaflet (IGL) and ventral lateral geniculate (vLGN) nucleus conveys light information to subcortical regions, adjusting visuomotor, and circadian functions. It is noteworthy that several visual related cells, such as neuronal subpopulations in the IGL and vLGN are neurochemically characterized by the presence of calcium binding proteins. Calretinin (CR), a representative of such proteins, denotes region-specificity in a temporal manner by variable day–night expression. In parallel, age-related brain dysfunction and neurodegeneration are associated with abnormal intracellular concentrations of calcium. Here, we investigated whether daily changes in the number of CR neurons are a feature of the aged IGL and vLGN in rats. To this end, we perfused rats, ranging from 3 to 24 months of age, within distinct phases of the day, namely zeitgeber times (ZTs). Then, we evaluated CR immunolabeling through design-based stereological cell estimation. We observed distinct daily rhythms of CR expression in the IGL and in both the retinorecipient (vLGNe) and non-retinorecipient (vLGNi) portions of the vLGN. In the ZT 6, the middle of the light phase, the CR cells are reduced with aging in the IGL and vLGNe. In the ZT 12, the transition between light to dark, an age-related CR loss was found in all nuclei. While CR expression predominates in specific spatial domains of vLGN, age-related changes appear not to be restricted at particular portions. No alterations were found in the dark/light transition or in the middle of the dark phase, ZTs 0, and 18, respectively. These results are relevant in the understanding of how aging shifts the phenotype of visual related cells at topographically organized channels of visuomotor and circadian processing.


2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Alexander Benz ◽  
Hugo A Katus ◽  
David Hassel

The most common outcome of heart failure (HF) is sudden cardiac death which results mostly from prolonged action potential duration (APD) and arrhythmias. During the pathogenesis and progression of HF, a vast number of signaling pathways are altered. microRNAs are small noncoding RNAs that post-transcriptionally finetune gene expression. Interestingly, several microRNAs are dysregulated during HF, suggesting a potential involvement in the development and progression of the disease. Here, we identified miR-19 as an important regulator of heart function. Zebrafish lacking miR-19 developed severe bradycardia and reduced cardiac contractility. While the mammalian genome encodes for two isoforms of miR-19, zebrafish express four members (19a-d). We found that the reduction of miR-19b specifically is sufficient to cause bradycardia and reduced cardiac contractility. Imaging of ventricular APs from whole hearts revealed that APD is significantly prolonged and repolarization is impaired in miR-19b deficient zebrafish. By qRT-PCR experiments we showed that the expression of several cardiac ion channels is altered. Moreover, miR-19b deficiency results in increased sensitivity to an AV-Block, which is a characteristic feature of long QT-Syndrome in zebrafish. In conclusion, we identified miR-19b as a novel and essential modulator of the electrical activity of the heart and establish miR-19b as a potential candidate gene causative for human long QT syndrome.


2020 ◽  
Vol 9 (3) ◽  
pp. 818 ◽  
Author(s):  
Vera Gallo ◽  
Emilia Cirillo ◽  
Rosaria Prencipe ◽  
Alessio Lepore ◽  
Luigi Del Vecchio ◽  
...  

Very high IgM levels represent the hallmark of hyper IgM (HIGM) syndromes, a group of primary immunodeficiencies (PIDs) characterized by susceptibility to infections and malignancies. Other PIDs not fulfilling the diagnostic criteria for HIGM syndromes can also be characterized by high IgM levels and susceptibility to malignancies. The aim of this study is to characterize clinical phenotype, immune impairment, and pathogenic mechanism in six patients with very high IgM levels in whom classical HIGM syndromes were ruled out. The immunological analysis included extended B-cell immunophenotyping, evaluation of class switch recombination and somatic hypermutation, and next generation sequencing (NGS). Recurrent or severe infections and chronic lung changes at the diagnosis were reported in five out of six and two out of six patients, respectively. Five out of six patients showed signs of lymphoproliferation and four patients developed malignancies. Four patients showed impaired B-cell homeostasis. Class switch recombination was functional in vivo in all patients. NGS revealed, in one case, a pathogenic mutation in PIK3R1. In a second case, the ITPKB gene, implicated in B- and T-cell development, survival, and activity was identified as a potential candidate gene. Independent of the genetic basis, very high IgM levels represent a risk factor for the development of recurrent infections leading to chronic lung changes, lymphoproliferation, and high risk of malignancies.


1985 ◽  
Vol 248 (4) ◽  
pp. R434-R438 ◽  
Author(s):  
H. E. Albers ◽  
L. Yogev ◽  
R. B. Todd ◽  
B. D. Goldman

The 24-h patterns of circulating cortisol and corticosterone were determined in male hamsters housed under a 14:10 light-dark cycle. Corticoid levels varied significantly over the 24-h sampling period with peak levels of both hormones occurring near the onset of the daily dark phase. The ratio of cortisol to corticosterone changed dramatically during the day. Corticosterone levels were significantly higher than cortisol during the early part of the light phase; however, cortisol levels became significantly higher than corticosterone when both hormones began their daily rise. To examine whether the circadian rhythm of cortisol secretion could be involved in the physiological control of hamster circadian organization, cortisol was infused at approximately physiological levels into adrenalectomized hamsters either continuously or in a 24-h rhythm. No significant differences were observed in the timing of circadian wheel-running rhythms in hamsters housed in LD 16:8, LD 14:10, or LL when cortisol was infused continuously, in a 24-h rhythm that mimicked the cortisol rhythm of intact hamsters, or in a 24-h rhythm several hours out of phase with the rhythm of intact hamsters. Provision of cortisol in a 24-h rhythm appeared to promote the survival of adrenalectomized hamsters since hamsters receiving a 24-h pattern of cortisol survived the experimental protocol significantly longer than those receiving the same dose of cortisol continuously.


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