scholarly journals Time matters: pathological effects of repeated psychosocial stress during the active, but not inactive, phase of male mice

2012 ◽  
Vol 215 (3) ◽  
pp. 425-437 ◽  
Author(s):  
Manuela S Bartlang ◽  
Inga D Neumann ◽  
David A Slattery ◽  
Nicole Uschold-Schmidt ◽  
Dominik Kraus ◽  
...  

Recent findings in rats indicated that the physiological consequences of repeated restraint stress are dependent on the time of day of stressor exposure. To investigate whether this is also true for clinically more relevant psychosocial stressors and whether repeated stressor exposure during the light phase or dark phase is more detrimental for an organism, we exposed male C57BL/6 mice to social defeat (SD) across 19 days either in the light phase between Zeitgeber time (ZT)1 and ZT3 (SDL mice) or in the dark phase between ZT13 and ZT15 (SDD mice). While SDL mice showed a prolonged increase in adrenal weight and an attenuated adrenal responsiveness to ACTHin vitroafter stressor termination, SDD mice showed reduced dark phase home-cage activity on observation days 7, 14, and 20, flattening of the diurnal corticosterone rhythm, lack of social preference, and higherin vitroIFNγ secretion from mesenteric lymph node cells on day 20/21. Furthermore, the colitis-aggravating effect of SD was more pronounced in SDD than SDL mice following dextran sulfate sodium treatment. In conclusion, the present findings demonstrate that repeated SD effects on behavior, physiology, and immunology strongly depend on the time of day of stressor exposure. Whereas physiological parameters were more affected by SD during the light/inactive phase of mice, behavioral and immunological parameters were more affected by SD during the dark phase. Our results imply that repeated daily SD exposure has a more negative outcome when applied during the dark/active phase. By contrast, the minor physiological changes seen in SDL mice might represent beneficial adaptations preventing the formation of those maladaptive consequences.


1986 ◽  
Vol 64 (11) ◽  
pp. 2608-2616 ◽  
Author(s):  
Jean-Claude Fournioux ◽  
Roger Bessis

Two different types of morphogenesis are induced in vitro in the grapevine by changing the system of sealing the culture tubes (with or without Parafilm). The differences appear mainly in the degree of miniaturiation: the plants the most miniaturized, those with Parafilm, have all the characteristics of an immature juvenile state. The others, without Parafilm, show an intermediate morphology between the adult and the juvenile forms. It follows then that the importance of juvenile characters is linked to the degree of miniaturization. One of the effects of Parafilm is in the modification of the amount of CO2 in the atmosphere of the tubes: in excess during the dark phase and in severe shortage during the light phase. We have found then, that among all the environmental factors which could influence the morphogenesis of the grapevine in vitro, CO2 appears to play a relatively important role.



2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Elisa M. Fonseca ◽  
Mariane C. Vicente ◽  
Stephanie Fournier ◽  
Richard Kinkead ◽  
Kênia C. Bícego ◽  
...  

AbstractLight/dark cycle affects the physiology of vertebrates and hypothalamic orexin neurons (ORX) are involved in this function. The breathing pattern of the green iguana changes from continuous to episodic across the light/dark phases. Since the stimulatory actions of ORX on breathing are most important during arousal, we hypothesized that ORX regulates changes of breathing pattern in iguanas. Thus, we: (1) Localized ORX neurons with immunohistochemistry; (2) Quantified cyclic changes in plasma orexin-A levels by ELISA; (3) Compared breathing pattern at rest and during hypoxia and hypercarbia; (4) Evaluated the participation of the ORX receptors in ventilation with intracerebroventricular microinjections of ORX antagonists during light and dark phases. We show that the ORX neurons of I. iguana are located in the periventricular hypothalamic nucleus. Orexin-A peaks during the light/active phase and breathing parallels these cyclic changes: ventilation is higher during the light phase than during the dark phase. However, inactivation of ORX-receptors does not affect the breathing pattern. Iguanas increase ventilation during hypoxia only during the light phase. Conversely, CO2 promotes post-hypercarbic hyperpnea during both phases. We conclude that ORXs potentiate the post-hypercarbic (but not the hypoxic)-drive to breathe and are not involved in light/dark changes in the breathing pattern.



Behaviour ◽  
2014 ◽  
Vol 151 (14) ◽  
pp. 1943-1966 ◽  
Author(s):  
Cássio M. Loss ◽  
Sandro D. Córdova ◽  
Sidia Maria Callegari-Jacques ◽  
Diogo L. de Oliveira

It is well known that rats exhibit elevated levels of activity during the dark phase and reduced levels during the light phase of the photoperiod cycle. However, the information about the influence of the time-of-day on the strategies used to explore the environment is still not understood. Here we tested the hypothesis that time-of-day influences the fine-scale exploratory behaviour of rats, measured in the open field (OF) test, and emotionality of rats, measured in the elevated plus maze (EPM) test. Adult male Wistar rats were subjected to the OF and EPM tests during Morning, Afternoon, or Evening sessions. In the OF, a principal component analysis (PCA) revealed that the Evening group exhibited longer duration of locomotion and rearing, and also higher distance travelled, trip length, inter-stop distance, number of stops and stops per trip compared to other groups. PCA also revealed that the Evening group exhibited shorter time spent at the home base, duration of locomotion along the perimeter and distance travelled along the perimeter compared to other groups. In the EPM test, there was no difference between the groups in any of the parameters evaluated. Our results indicate that the time-of-day may influence the spatio-temporal organization of exploration of rats subjected to unfamiliar environments. These alterations appear to be unrelated to differences in the emotional state of the animals.



2013 ◽  
Vol 305 (3) ◽  
pp. R271-R280 ◽  
Author(s):  
Michael D. Schwartz ◽  
Jessica A. Mong

Ovarian hormones are thought to modulate sleep and fluctuations in the hormonal milieu are coincident with sleep complaints in women. In female rats, estradiol increases waking and suppresses sleep. In this study, we asked whether this effect is mediated via circadian or homeostatic regulatory mechanisms. Ovariectomized female rats received daily injections of estradiol benzoate (EB) or sesame oil that mimicked the rapid increase and subsequent decline of circulating estradiol at proestrus. In one experiment, animals were sleep deprived for 6 h starting at lights-on, so that recovery began in the mid-light phase; in the second experiment, animals were sleep deprived starting in the mid-light phase, so that recovery began at lights-off. EB suppressed baseline rapid eye movement (REM) and non-REM (NREM) sleep and increased waking in the dark phase. In both experiments, EB enhanced REM recovery in the light phase while suppressing it in the dark compared with oil; this effect was most pronounced in the first 6 h of recovery. By contrast, NREM recovery was largely unaffected by EB. In summary, EB enhanced waking and suppressed sleep, particularly REM sleep, in the dark under baseline and recovery conditions. These strong temporally dependent effects suggest that EB consolidates circadian sleep-wake rhythms in female rats.



Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 844
Author(s):  
Amanda J. Page

Gastrointestinal vagal afferents (VAs) play an important role in food intake regulation, providing the brain with information on the amount and nutrient composition of a meal. This is processed, eventually leading to meal termination. The response of gastric VAs, to food-related stimuli, is under circadian control and fluctuates depending on the time of day. These rhythms are highly correlated with meal size, with a nadir in VA sensitivity and increase in meal size during the dark phase and a peak in sensitivity and decrease in meal size during the light phase in mice. These rhythms are disrupted in diet-induced obesity and simulated shift work conditions and associated with disrupted food intake patterns. In diet-induced obesity the dampened responses during the light phase are not simply reversed by reverting back to a normal diet. However, time restricted feeding prevents loss of diurnal rhythms in VA signalling in high fat diet-fed mice and, therefore, provides a potential strategy to reset diurnal rhythms in VA signalling to a pre-obese phenotype. This review discusses the role of the circadian system in the regulation of gastrointestinal VA signals and the impact of factors, such as diet-induced obesity and shift work, on these rhythms.



1986 ◽  
Vol 235 (1) ◽  
pp. 19-24 ◽  
Author(s):  
G F Gibbons ◽  
C P Attwell Thomas ◽  
C R Pullinger

The effect of (-)-hydroxycitrate on the conversion of [1-14C]oleate into cholesterol was dependent on the time of day at which the cells were prepared and on the extracellular oleate concentration. In hepatocytes prepared during the light phase of the diurnal cycle (L2-hepatocytes), (-)-hydroxycitrate inhibited the conversion of L-[U-14C]lactate (2 mM) and of 0.13 mM-[1-14C]oleate into cholesterol. However, when [1-14C]oleate was present at 1.3 mM, most of the sterol carbon was derived from this source, and under these conditions (-)-hydroxycitrate had no inhibitory effect on [14C]cholesterol formation. In these cells, non-radioactive acetoacetate blocked the conversion of 1.3 mM-[1-14C]oleate, but not of 0.13 mM-[1-14C]oleate, into cholesterol. In cells prepared during the dark phase of the diurnal cycle (D6-hepatocytes), irrespective of the concentration of [1-14C]oleate, (-)-hydroxycitrate decreased its conversion into cholesterol. In both types of cell preparation, the inhibitory effect of (-)-hydroxycitrate on the conversion of L-[U-14C]lactate into cholesterol was greater than that on the overall rate of cholesterol production from all endogenous sources. These results provide evidence for the following. (1) The major metabolic route by which oleate is converted into cholesterol is dependent on its extracellular concentration. (2) When oleate is the major source of hepatic sterol carbon, the flux of substrate through citrate into cholesterol is dependent on the nutritional state of the animal. (3) When endogenous substrates are the sole source of sterol carbon, a substantial proportion of the carbon enters the cholesterol pathway through routes not involving citrate cleavage.



2021 ◽  
Author(s):  
Bianca Viberti ◽  
Lisa Branca ◽  
Simone Bellini ◽  
Claudio LA Bassetti ◽  
Antoine Adamantidis ◽  
...  

Narcolepsy is characterized by increased REM sleep propensity and cataplexy. Although narcolepsy is caused by the selective loss or dysfunction of hypocretin (Hcrt) neurons within the lateral hypothalamus (LH), mechanisms underlying REM sleep propensity and cataplexy remain to be elucidated. We have recently shown that wild type (WT) mice increase REM sleep expression when exposed to thermoneutral ambient temperature (Ta) warming during the light (inactive) phase. We hypothesized that the loss of Hcrt may lead to exaggerated responses with respect to increased REM sleep and cataplexy during Ta warming. To test this hypothesis, Hcrt-KO mice were implanted for chronic sleep recordings and housed in a temperature-controlled cabinet. Sleep-wake expression and both spontaneous cataplexy and food-elicited cataplexy were evaluated at constant Ta and during a Ta manipulation protocol. Here we show several unexpected findings. First, Hcrt-KO mice show opposite circadian patterns with respect to REM sleep responsiveness to thermoneutral Ta warming compared to WT mice. As previously demonstrated, WT mice increased REM sleep when Ta warming is presented during the inactive (light) phase, whereas Hcrt-KO showed a significant decrease in REM sleep expression. In contrast, Hcrt-KO mice increased REM sleep expression upon exposure to Ta warming when presented during the active (dark) phase, a circadian time when WT mice showed no significant changes in REM sleep as a function of Ta. Second, we found that REM sleep and cataplexy can be dissociated through Ta manipulation. Specifically, although Ta warming significantly increased REM sleep expression in Hcrt-KO mice during the active phase, cataplexy bout number and total cataplexy duration significantly decreased. In contrast, cataplexy expression was favoured during Ta cooling when REM sleep expression significantly decreased. Finally, video actigraphy and sleep-wake recordings in Hcrt-KO mice demonstrated that Ta manipulation did not significantly alter waking motor activity patterns or waking or NREM sleep durations. These data suggest that neural circuits gating REM sleep and cataplexy expression can be dissociated with Ta manipulation.



1980 ◽  
Vol 58 (10) ◽  
pp. 1174-1179 ◽  
Author(s):  
Y. Isobe ◽  
S. Takaba ◽  
K. Ohara

Effects of photoperiod on heat resistance were studied in 88 rats by observing their survival times in a hot environment (42.5 °C). Prior to the experiments individual rats were exposed to a given heat (42.5 °C) at a definite time of day and a "predicted survial time" in a given heat in individual rats was obtained. Rats were then divided into eight groups (with nine rats in each group) so as to ensure intergroup homogeneity regarding their predicted survival time and were exposed to heat at different times of day (every 3 h) until they were exhausted.It was found that the heat resistance varied with the time of day. In the eight groups kept under a normal light–dark cycle (L, 0700–1900; D, 1900–0700), heat resistances were observed to be significantly higher in the light phase than in the dark phase. Lethal body temperature was not correlated with the heat resistance. In two other groups (n = 8) kept under conditions reversed from the normal lighting cycle, resistance was higher in the nighttime (corresponding to the light phase when the rats were kept in the reversed lighting cycle) than in the morning (corresponding to the dark phase), these changes being accompanied by a phase shift of the diurnal changes in body temperature.



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.



Genetics ◽  
2000 ◽  
Vol 154 (3) ◽  
pp. 1181-1192 ◽  
Author(s):  
Laura E Waggoner ◽  
Laura Anne Hardaker ◽  
Steven Golik ◽  
William R Schafer

Abstract Egg-laying behavior in the nematode Caenorhabditis elegans involves fluctuation between alternative behavioral states: an inactive state, during which eggs are retained in the uterus, and an active state, during which eggs are laid in bursts. We have found that the flp-1 gene, which encodes a group of structurally related neuropeptides, functions specifically to promote the switch from the inactive to the active egg-laying state. Recessive mutations in flp-1 caused a significant increase in the duration of the inactive phase, yet egg-laying within the active phase was normal. This pattern resembled that previously observed in mutants defective in the biosynthesis of serotonin, a neuromodulator implicated in induction of the active phase. Although flp-1 mutants were sensitive to stimulation of egg-laying by serotonin, the magnitude of their serotonin response was abnormally low. Thus, the flp-1-encoded peptides and serotonin function most likely function in concert to facilitate the onset of the active egg-laying phase. Interestingly, we observed that flp-1 is necessary for animals to down-regulate their rate of egg-laying in the absence of food. Because flp-1 is known to be expressed in interneurons that are postsynaptic to a variety of chemosensory cells, the FLP-1 peptides may function to regulate the activity of the egg-laying circuitry in response to sensory cues.



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