In a Rat Model of Night Work, Activity during the Normal Resting Phase Produces Desynchrony in the Hypothalamus

Abstract

Internal synchrony among external cycles and internal oscillators allows adaptation of physiology to cyclic demands for homeostasis. Night work and shift work lead to a disrupted phase relationship between external time cues and internal rhythms, also losing internal coherence among oscillations. This process results in internal desynchrony (ID) in which behavioral, hormonal, and metabolic variables cycle out of phase. It is still not clear whether ID originates at a peripheral or at a central level. In order to determine the possible role of hypothalamic oscillators in ID, we explored with a rat model of "night work" daily rhythms of activity and clock gene expression in the hypothalamus. This study provides evidence that wakefulness and activity during the normal resting phase lead to a shift in the diurnal rhythms of c-Fos and induce a rhythm of PER1 in the arcuate and dorsomedial nucleus of the hypothalamus, both associated with metabolism and regulation of the sleep/wake cycle. Moreover, the number of orexin (ORX)-positive neurons and c-Fos in the perifornical area increased during the working period, suggesting a relevant switch of activity in this brain region induced by the scheduled activity; however, the colocalization of c-Fos in ORX-positive cells was not increased. In contrast, the suprachiasmatic nucleus and the paraventricular nucleus remained locked to the light/dark cycle, resulting in ID in the hypothalamus. Present data suggest that ID occurs already at the level of the first output projections from the SCN, relaying nuclei that transmit temporal signals to other brain areas and to the periphery.

White Adipose Tissue and Circadian Rhythm Dysfunctions in Obesity: Pathogenesis and Available Therapies

“…Additionally, rats submitted to forced activity during the sleeping phase, showed altered temporal pattern of food intake, loss of glucose rhythmicity and a reversed rhythm of triacylglycerol levels, though CNS activity was intact. Similarly, in night workers the combination of altered work and eating activities, may lead to internal desynchronization by uncoupling metabolic functions from the biological clock which remained fixed to the LD cycle [74,75,79,80] . Furthermore, feeding mice at the wrong time (inactive or sleeping phase), desynchronizes peripheral clocks and causes obesity by inducing hyperphagia, physical inactivity, LEP resistance, hepatic lipid accumulation, and hyperadiposity.…”

Consequences of circadian dysregulation on metabolism

“…74 Forced activity during an 8-hour window of the inactive phase increases body mass, flattens glucose rhythms, alters glucose tolerance, shifts the peak in serum triglycerides to the daytime, and overall alters rhythmicity in the hypothalamus and the liver. [75][76][77] Nighttime food restriction in rats exposed to this forced activity protocol restores glucose rhythms and baseline body mass. 75 Approximately 20% of the global population works in night shifts, forcing individuals to be physically, mentally, and metabolically active out of circadian phase.…”

The Impact of Toxic Stress on the Morphofunctional State of the Hypothalamic Arcuate Nucleus in the Conditions of the Changed Mode of Light Exposure

“…В условиях естественного освеще-ния к токсиканту оказались более резистент-ны особи женского пола, что согласуется с литературными данными, полученными как для кадмия, так и для других тяжелых метал-лов [8,9]. За половые различия в реакции на токсический стресс считают ответственными половые гормоны, подобные прогестерону и β-эстрадиолу [10], рецепторы к которым имеют различную плотность в аркуатном ядре гипоталамуса самцов и самок [11].…”