Chronodisruption
Irregular daily regime with sleep deprivation and eating schedules misaligned with light-dark cycle disrupt the circadian system. The project studies one of the potential mechanisms of how these factors may negatively affect health. In mammals, only the central clock in the suprachiasmatic nucleus (SCN) of the hypothalamus receives information about the light/dark (LD) cycle to synchronize with external time and entrain the clocks in other tissues, both in the brain and on the periphery. Unlike the SCN, these downstream clocks are also more or less sensitive to timing of food. Chronodisruption (CD) caused by a misalignment between the LD cycle, sleep/wake, and feeding/fasting cycles is the major contributor to the uncoupling of the peripheral clocks from the SCN. One of the downstream clocks is in the choroid plexus.
Choroid plexus
Choroid plexus (ChP) is a non-neural brain structure in brain ventricles and the main source of cerebrospinal fluid (CSF). ChP has recently attracted significant attention in the neuroscience field due to its involvement in brain homeostasis and the pathophysiology of neuropsychiatric disorders. Our recent data show that ChP clock is highly sensitive to CD, feeding and glucocorticoids. Therefore, the objective of this project is to provide mechanistic insights into how CD affects the circadian regulation of the ChP physiological functions. Specifically, we hypothesize that CD impairs the CSF production, composition and brain waste clearance via the ChP clock and that feeding regime can ameliorate its negative impact. Because both the prevalence of brain disorders and the circadian clock in ChP are sexually dimorphic, a factor of biological sex is taken into account.
Practical impact
A high percentage of people are struggling with mental health problems due to the pressure that current society places on human health. There is an increasing need for exploring novel mechanisms that can develop strategies to prevent mental disorders. Human lifestyle, with its irregular daily regime that disrupts circadian organization, has been recognized as a significant factor in the increase of neuropsychiatric disorders, but the mechanism is poorly understood. The project addresses this topical issue.
Fig. Heatmap of ChP transcriptome data. ChP were collected every four h over a 48 h period from C57Bl/6J mice released into constant darkness, which had intact SCN (control), or their SCN was surgically removed (SCNx). From Sladek et al. 2024
Choroid plexus, a non-neural brain structure in brain ventricles producing CSF by active filtration of blood, contains a high amplitude circadian clock that rhythmically regulates its physiological functions. The video shows PER2 protein, one of the clock genes that form the circadian clock in each cell, as its levels cycle for 7 days ex vivo with circa 24h period..
