Cognitive function and brain plasticity in a rat model of shift work: role of daily rhythms, sleep and glucocorticoids

Abstract

Many occupations require operations during the night-time when the internal circadian clock promotes sleep, in many cases resulting in impairments in cognitive performance and brain functioning. Here, we use a rat model to attempt to identify the biological mechanisms underlying such impaired performance. Rats were exposed to forced activity, either in their rest-phase (simulating night-shift work; rest work) or in their active-phase (simulating day-shift work; active work). Sleep, wakefulness and body temperature rhythm were monitored throughout. following three work shifts, spatial memory performance was tested on the Morris Water Maze task. After 4 weeks washout, the work protocol was repeated, and blood and brain tissue collected. Simulated night-shift work impaired spatial memory and altered biochemical markers of cerebral cortical protein synthesis. Measures of daily rhythm strength were blunted, and sleep drive increased. individual variation in the data suggested differences in shift work tolerance. Hierarchical regression analyses revealed that type of work, changes in daily rhythmicity and changes in sleep drive predict spatial memory performance and expression of brain protein synthesis regulators. Moreover, serum corticosterone levels predicted expression of brain protein synthesis regulators. These findings open new research avenues into the biological mechanisms that underlie individual variation in shift work tolerance. We live in a 24-h society, where services are required around the clock. For this reason, a significant proportion of the work force is required to work shifts. The temporal aspects of the work schedule, night shift work in particular, has negative consequences for cognitive functioning. The risk of errors and accidents is increased on the night shift compared to morning and afternoon shifts, and the risk increases across consecutive night shifts worked 1,2. It has long been assumed that the cause for cognitive dysfunction on the night shift is lack of sleep, and the link between perturbed sleep and cognitive dysfunction is well documented 3,4. In the case of night shift work, both homeostatic and circadian aspects of sleep are challenged. Workers are required to stay awake for prolonged hours at times of day when the circadian system promotes rest, and to sleep at times when the circadian system promotes wakefulness 5,6. In addition to disturbed sleep and circadian rhythm regulation, night shift work can act as a stressor on bodily systems, which may result in adverse health effects. Both acute sleep deprivation and chronic sleep restriction are known to induce neuroendocrine stress, as evidenced by elevated activity in the hypothalamic-pituitary-adrenal (HPA) axis, resulting in increased levels of circulating corticosteroids 7. Night shift work has been shown to alter the daily rhythm of circulating corticosteroids in both laboratory and field studies 8-10. Disturbances in circadian organization not only disrupt sleep and circulating corticosteroids, but also many other biological...

Exogenous melatonin decreases circadian misalignment and body weight among early types

“…This study is a phase II clinical trial, which limits generalizability to a larger population. Individual variability in tolerance for shift work 67 was also not evaluated in this study and should be taken into account before prescribing exogenous melatonin. However, the longitudinal crossover design in real-life conditions is the strength of this study.…”

Brain structural correlates of subjective sleepiness and insomnia symptoms in shift workers

“…The putamen is a known site of synaptic plasticity ( Kreitzer and Malenka, 2008 ), and it has been reported that circadian rhythms affect the plasticity of putamen ( Elmenhorst et al, 2016 ). Animal studies have demonstrated that simulated shift work impairs the synthesis of proteins related to synaptic plasticity ( Marti et al, 2017 , 2020 ). A decrease in the level of melatonin in shift workers ( Wei et al, 2020 ) may contribute to the impaired neuroplasticity in this group, as melatonin is known to stimulate all stages of neuroplasticity ( Valdés-Tovar et al, 2018 ).…”

Long-lasting effects of disturbing the circadian rhythm or sleep in adolescence

“…One such example of chronic circadian disruption occurs in shift work, which puts individuals at a higher risk for cardiovascular disease, diabetes, affective disorders, obesity, fertility issues, cancer, and more ( Costa, 2010 ). Rodents that underwent a paradigm mimicking human shift work also showed many of these same negative and persistent effects ( Marti et al, 2020 ; Banks et al, 2022 ).…”