Melatonin alleviates circadian system disruption induced by chronic shifts of the light‐dark cycle in Octodon degus

Abstract

Modern 24-h society lifestyle is associated with experiencing frequent shifts in the lighting conditions which can negatively impact human health. Here, we use the degus, a species exhibiting diurnal and nocturnal chronotypes, to: (a) assess the impact of chronic shifts of the light:dark (LD) cycle in the animal's physiology and behaviour and (b) test the therapeutic potential of melatonin in enhancing rhythmicity under these conditions. Degus were subjected to a "5d + 2d" LD-shifting schedule for 19 weeks. This protocol aims to mimic lighting conditions experienced by humans during shift work: LD cycle was weekly delayed by 8h during 5 "working" days (Morning, Afternoon and Night schedule); during weekends (2 days), animals were kept under Morning schedule. After 9 weeks, melatonin was provided daily for 6h in the drinking water. The "5d + 2d" shifting LD schedule led to a disruption in wheel-running activity (WRA) and body temperature (Tb) rhythms which manifested up to three separate periods in the circadian range. This chronodisruption was more evident in nocturnal than in diurnal degus, particularly during the Afternoon schedule when a phase misalignment between WRA and Tb rhythms appeared. Melatonin treatment and, to a lesser extent, water restriction enhanced the 24-h component, suggesting a potential role in ameliorating the disruptive effects of shift work. K E Y W O R D Sbody temperature rhythm, chronotype, circadian disruption, degu, diurnal, melatonin, shift work

The E3 ubiquitin ligase adaptor Tango10 links the core circadian clock to neuropeptide and behavioral rhythms

“…Here, we used an implementation of a variational DA algorithm previously applied to fit models to current-clamp data from SCN neurons (see ref. 77 for a detailed description of our implementation and its mathematical representation). This approach can simultaneously estimate the mean trajectory of the state variables ( V , m , and h ) and parameters of our model.…”

“…The fact that each time point included increases the dimension of the optimization problem, combined with the high sampling rate (10 kHz) required for current-clamp experiments to accurately capture AP waveforms, means that only a relatively small amount of data (a few seconds at most) can be assimilated before the optimization problem becomes too large to be solved. To increase the amount of information contained in these short windows of data, previous work with DA- and conductance-based models have utilized current-clamp recordings performed with complex time-varying stimuli ( 79 ) or a series of current pulses ( 77 ). In this work, we are able to fit models with DA in the absence of input currents to stimulate the neuron (i.e., using spontaneous firing activity alone).…”

Widespread Doublecortin Expression in the Cerebral Cortex of the Octodon degus

“…The diurnal rodent Octodon degus has been found to be suitable model to investigate diurnal rhythm ( Jiao et al, 1999 ; Ocampo-Garcés et al, 2005 ; Hummer et al, 2007 ; Vivanco et al, 2007 , 2010a , b ; Otalora et al, 2010 ; Bonmati-Carrion et al, 2017 ; Baño-Otálora et al, 2020 ), cognitive functions ( Okanoya et al, 2008 ; Popović et al, 2010 ; Uekita and Okanoya, 2011 ; Pereda-Pérez et al, 2013 ; Tarragon et al, 2014 ), social interactions ( Braun et al, 2003 ; Ziabreva et al, 2003 ; Lee, 2004 ; Poeggel et al, 2005 ; Colonnello et al, 2011 ), age-related neuropathology, and behavioral alterations ( Inestrosa et al, 2005 ; Popović et al, 2009 ; van Groen et al, 2011 ; Braidy et al, 2012 ) as well as hippocampal neurogenesis ( Kumazawa-Manita et al, 2013a ; Akers et al, 2014 ). Akers et al (2014) demonstrated modest reduction in proliferating Ki67 + cells and immature doublecortin (DCX) positive neurons in dentate gyrus (DG) of infant degus and guinea pigs in comparison to mice.…”

Possible role of exogenous melatonin in preventing more serious COVID-19 infection in patients with type 2 diabetes mellitus

“…In this context, melatonin with its anti-inflammatory properties can be a promising drug. In addition to its direct anti-inflammatory activity 7,8 , melatonin can treat sleep disorders common in these patients [9][10][11][12] which would further contribute to reducing baseline inflammation. In this article, we will discuss the pathophysiological basis and perspectives for the prophylactic use of melatonin to prevent severe forms of COVID-19 in patients with DM2.…”