bims-ciryme 2022-02-13 papers

Front Neurosci. 2021 ;15 765850

The Suprachiasmatic Nucleus Regulates Anxiety-Like Behavior in Mice.

Chelsea A Vadnie, Kaitlyn A Petersen, Lauren A Eberhardt, Mariah A Hildebrand, Allison J Cerwensky, Hui Zhang, Jennifer N Burns, Darius D Becker-Krail, Lauren M DePoy, Ryan W Logan, Colleen A McClung.

Individuals suffering from mood and anxiety disorders often show significant disturbances in sleep and circadian rhythms. Animal studies indicate that circadian rhythm disruption can cause increased depressive- and anxiety-like behavior, but the underlying mechanisms are unclear. One potential mechanism to explain how circadian rhythms are contributing to mood and anxiety disorders is through dysregulation of the suprachiasmatic nucleus (SCN) of the hypothalamus, known as the "central pacemaker." To investigate the role of the SCN in regulating depressive- and anxiety-like behavior in mice, we chronically manipulated the neural activity of the SCN using two optogenetic stimulation paradigms. As expected, chronic stimulation of the SCN late in the active phase (circadian time 21, CT21) resulted in a shortened period and dampened amplitude of homecage activity rhythms. We also repeatedly stimulated the SCN at unpredictable times during the active phase of mice when SCN firing rates are normally low. This resulted in dampened, fragmented, and unstable homecage activity rhythms. In both chronic SCN optogenetic stimulation paradigms, dampened homecage activity rhythms (decreased amplitude) were directly correlated with increased measures of anxiety-like behavior. In contrast, we only observed a correlation between behavioral despair and homecage activity amplitude in mice stimulated at CT21. Surprisingly, the change in period of homecage activity rhythms was not directly associated with anxiety- or depressive-like behavior. Finally, to determine if anxiety-like behavior is affected during a single SCN stimulation session, we acutely stimulated the SCN in the active phase (zeitgeber time 14-16, ZT14-16) during behavioral testing. Unexpectedly this also resulted in increased anxiety-like behavior. Taken together, these results indicate that SCN-mediated dampening of rhythms is directly correlated with increased anxiety-like behavior. This work is an important step in understanding how specific SCN neural activity disruptions affect depressive- and anxiety-related behavior.

Keywords: amplitude; anxiety; circadian rhythms; mice; optogenetics; suprachiasmatic nucleus

DOI: https://doi.org/10.3389/fnins.2021.765850

Nat Methods. 2022 Feb;19(2): 231-241

A genetically encoded sensor for in vivo imaging of orexin neuropeptides.

Orexins (also called hypocretins) are hypothalamic neuropeptides that carry out essential functions in the central nervous system; however, little is known about their release and range of action in vivo owing to the limited resolution of current detection technologies. Here we developed a genetically encoded orexin sensor (OxLight1) based on the engineering of circularly permutated green fluorescent protein into the human type-2 orexin receptor. In mice OxLight1 detects optogenetically evoked release of endogenous orexins in vivo with high sensitivity. Photometry recordings of OxLight1 in mice show rapid orexin release associated with spontaneous running behavior, acute stress and sleep-to-wake transitions in different brain areas. Moreover, two-photon imaging of OxLight1 reveals orexin release in layer 2/3 of the mouse somatosensory cortex during emergence from anesthesia. Thus, OxLight1 enables sensitive and direct optical detection of orexin neuropeptides with high spatiotemporal resolution in living animals.

DOI: https://doi.org/10.1038/s41592-021-01390-2

J Pineal Res. 2022 Feb 08.

Unanticipated daytime melatonin secretion on a simulated night shift schedule generates a distinctive 24-h melatonin rhythm with antiphasic daytime and nighttime peaks.

Jingyi Qian, Christopher J Morris, Andrew Jk Phillips, Peng Li, Shadab A Rahman, Wei Wang, Kun Hu, Josephine Arendt, Charles A Czeisler, Frank Ajl Scheer.

The daily rhythm of plasma melatonin concentrations is typically unimodal, with one broad peak during the circadian night and near-undetectable levels during the circadian day. Light at night acutely suppresses melatonin secretion and phase shifts its endogenous circadian rhythm. In contrast, exposure to darkness during the circadian day has not generally been reported to increase circulating melatonin concentrations acutely. Here, in a highly-controlled simulated night shift protocol with 12-h inverted behavioral/environmental cycles, we unexpectedly found that circulating melatonin levels were significantly increased during daytime sleep (P < 0.0001). This resulted in a secondary melatonin peak during the circadian day in addition to the primary peak during the circadian night, when sleep occurred during the circadian day following an overnight shift. This distinctive diurnal melatonin rhythm with antiphasic peaks could not be readily anticipated from the behavioral/environmental factors in the protocol (e.g., light exposure, posture, diet, activity) or from current mathematical model simulations of circadian pacemaker output. The observation therefore challenges our current understanding of underlying physiological mechanisms that regulate melatonin secretion. Interestingly, the increase in melatonin concentration observed during daytime sleep was positively correlated with the change in timing of melatonin nighttime peak (P = 0.0015), but not with the degree of light-induced melatonin suppression during nighttime wakefulness (P = 0.92). Both the increase in daytime melatonin concentrations and the change in the timing of the nighttime peak became larger after repeated exposure to simulated night shifts (P = 0.009 and P = 0.0001, respectively). Furthermore, we found that melatonin secretion during daytime sleep was positively associated with an increase in 24-h glucose and insulin levels during the night shift protocol (P = 0.014 and P = 0.027, respectively). Future studies are needed to elucidate the key factor(s) driving the unexpected daytime melatonin secretion and the melatonin rhythm with antiphasic peaks during shifted sleep/wake schedules, the underlying mechanisms of their relationship with glucose metabolism, and the relevance for diabetes risk among shift workers. This article is protected by copyright. All rights reserved.

Keywords: Melatonin; circadian pacemaker; glucose metabolism; night shift

DOI: https://doi.org/10.1111/jpi.12791

J Appl Physiol (1985). 2022 Feb 10.

The submariners' sleep study. A field investigation of sleep and circadian hormones during a 67-days submarine mission with a strict 6h-on/6h-off watch routine.

Martine Van Puyvelde, Gerard Rietjens, Pieter Helmhout, Olivier Mairesse, Jeroen Van Cutsem, Nathalie Pattyn.

The submarine working and living environment is an isolated, confined, and extreme (ICE) environment where a continuous on-watch is required to fulfill the tactical objectives. The current study examined whether a physiological and behavioral adjustment to an operational watch standing scheme occurred in terms of hormonal secretion (i.e., melatonin and cortisol) and sleep during a 67-days undersea mission. The crew followed a strict scheme of watch-on blocks at 0:00-06:00 h and at 12:00-18:00 h (group 1, diurnal sleep group) or watch-on blocks at 06:00-12:00 h and 18:00-24:00 h (group 2, nocturnal sleep group). We sampled saliva during the operational blocks over a 24h period at day 55 of the mission and collected sleep actigraphy data during the entire mission in 10 participants. Sleep showed a biphasic split pattern with significantly unequal distributions of total sleep time (TST) and sleep efficiency (SE) between the two sleeping blocks, i.e., one long and one short sleep bout. Melatonin secretion showed no adjustment at the end of the mission to the watch standing blocks, following an endogenous circadian rhythm independent from the social zeitgebers with indications of a phase shift. Cortisol secretion however matched the biphasic work-sleep shift routine. Human physiology does not fully obey operational needs and there are differences in adjustment between melatonin and cortisol. A watch standing schedule that provides a balance between physiology and operationality still needs to be established. The potential adaptation effects of bright light therapy and melatonin supplementation should be investigated in future research.

Keywords: circadian rhythm; cortisol; melatonin; sleep; submarine

DOI: https://doi.org/10.1152/japplphysiol.00130.2021

Sci Rep. 2022 Feb 07. 12(1): 2022

Night shift work characteristics are associated with several elevated metabolic risk factors and immune cell counts in a cross-sectional study.

Astrid A Streng, Bette Loef, Martijn E T Dollé, Gijsbertus T J van der Horst, Inês Chaves, Karin I Proper, Linda W M van Kerkhof.

Night shift work is associated with increased health risks. Here we examined the association of metabolic risk factors and immune cell counts, with both night shift work and particular characteristics thereof: frequency, duration and consecutive night shifts. We performed a cross-sectional study using data from 10,201 non-shift workers and 1062 night shift workers of the Lifelines Cohort study. Linear regression analyses, adjusted for demographic, lifestyle and occupational factors, were used to study associations of night shift work characteristics with metabolic risk factors and immune cell counts. Night shift workers had an increased BMI, waist circumference and immune cell counts compared to non-shift workers. This was especially seen in night shift workers who had a higher frequency of night shifts per month (≥ 5: BMI: B = 0.81 kg/m2 (95%-CI = 0.43-1.10); waist circumference: B = 1.58 cm (95%-Cl = 0.34-1.71; leukocytes: B = 0.19 × 109 cells/L (95%-CI = 0.04-0.34 × 109)) and worked more consecutive night shifts (> 3: BMI: B = 0.92 kg/m2 (95%-CI = 0.41-1.43); waist circumference: B = 1.85 cm (95%-Cl = 0.45-3.24); leukocytes: B = 0.32 × 109 cells/L (95%-CI = 0.09-0.55 × 109)). This association was less pronounced in long-term night shift workers (≥ 20 years). Our findings provide evidence for the association between night shift work characteristics and BMI, waist circumference and leukocytes (including, monocytes, lymphocytes, and basophil granulocytes).

DOI: https://doi.org/10.1038/s41598-022-06122-w