Biology subjects

Hoekstra, M. M. B.

Publications and source records attributed to Hoekstra, M. M. B..

4 recordsLinked to original sources

bioRxiv2026

Sleep-dependent modulation of thalamic brain temperature estimates in humans

Mammalian thermal physiology is geared towards dissipating heat during sleep. Brain temperature typically decreases during non-rapid-eye-movement (NREM) sleep in all mammalian species measured to date, yet non-invasive confirmation in healthy humans is lacking: the only available human study used invasive recordings in epileptic patients without a wake control condition. Magnetic resonance spectroscopy (MRS) enables brain temperature mapping non-invasively, using the temperature-sensitive chemical shift of water relative to N-Acetyl-Aspartate as an internal reference. First, we validated that with metabolite cycling (MC), a MRS approach that enables the simultaneous acquisition of metabolite and water information without conventional water suppression, can be used to determine estimates of brain temperature in an ex vivo sheep head. Next, we determined that by using a temporal resolution of ~4 minutes, we obtained high-quality spectra without losing excessive temporal resolution. We then re-analyzed an existing set of MRS data (acquired with the MC sequence) of the thalamus in young adults (n=9) who slept in the evening for up to 2 hours in the scanner, to assess sleep-evoked changes in estimates of brain temperature. Of the nine participants, five participants took part in the subsequent wake-only experiment, allowing to control for the potential impact of circadian time and body posture on estimates of brain temperature. Sleep-wake states were quantified with standard polysomnography, confirming that the participants managed to sleep in the scanner. On average, they spent 39.4+/-15.7 min in N2 sleep, 24.8+/-18.1 min in N3 sleep, 10.0+/-4.9 min in N1 sleep, and 37.0+/-19.6 min awake. Estimates of brain temperature were correlated across the sleep and wake-only experiment within the same participant (R^2=0.29, P<0.0001). When participants entered NREM sleep, estimates of brain temperature decreased by 0.2 degrees Celcius. Moreover, the deeper NREM sleep, the more pronounced the decrease in estimates of brain temperature (P=0.014). These data suggest that an evening nap consisting of NREM sleep decreases thalamic temperature. Considering the profound impact temperature can have on brain functioning, these brain temperature changes could be a pathway through which sleep impacts the brain.

neuroscience↗

bioRxiv2020

A Sub-Minute Resolution Prediction of Brain Temperature Based on Sleep-Wake State in the Mouse

While brain temperature is of neurobiological and clinical importance, it is still unclear which factors contribute to its daily dynamics and to what degree. We recorded cortical temperature in mice alongside sleep-wake state during 4 days including a 6h sleep deprivation, and developed a mathematical tool to simulate temperature based on the sleep-wake sequence. The model estimated temperature with remarkable precision accounting for 91% of its variance based on three main factors with the sleep-wake sequence accounting for most of the variance (74%) and time-of-day ( circadian) the least (9%). As third factor, prior wake prevalence, was discovered to up-regulate temperature, explaining 43% of the variance. With similar accuracy the model predicted cortical temperature in a second, independent cohort using the parameters optimized for the first. Our model corroborates the profound influence of sleep-wake state on brain temperature, and can help differentiate thermoregulatory from sleep-wake driven effects in experiments affecting both.

neuroscience↗

bioRxiv2020

The sleep-wake distribution contributes to the peripheral rhythms in PERIOD-2

In the mouse, Period-2 (Per2) expression in tissues peripheral to the suprachiasmatic nuclei (SCN) increases during sleep deprivation and at times of the day when animals are predominantly awake spontaneously, suggesting that the circadian sleep-wake distribution directly contributes to the daily rhythms in Per2. We found support for this hypothesis by recording sleep-wake state alongside PER2 bioluminescence in freely behaving mice, demonstrating that PER2 increases during spontaneous waking and decreases during sleep. The temporary reinstatement of PER2 rhythmicity in behaviorally arrhythmic SCN-lesioned mice submitted to daily recurring sleep deprivations substantiates our hypothesis. Mathematical modelling revealed that PER2 dynamics can be described by a damped harmonic oscillator driven by two forces: a sleep-wake-dependent force and a SCN-independent circadian force. Our work underscores the notion that in peripheral tissues the clock gene circuitry integrates sleep-wake information and could thereby contribute to behavioral adaptability to respond to homeostatic requirements.

physiology↗

bioRxiv2018

Cold Inducible RNA-binding protein (CIRBP) adjusts clock gene expression and REM sleep recovery after sleep deprivation

Sleep depriving mice affects clock gene expression, suggesting that these genes partake in sleep homeostasis. The mechanisms linking wakefulness to clock gene expression are, however, not well understood. We propose CIRBP because its rhythmic expression is i) sleep-wake driven and ii) necessary for high-amplitude clock gene expression in vitro. We therefore expect Cirbp knock-out (KO) mice to exhibit attenuated sleep-deprivation (SD) induced changes in clock gene expression, and consequently to differ in their sleep homeostatic regulation. Lack of CIRBP indeed blunted the SD-incurred changes in cortical expression of the clock gene Rev-erb whereas it amplified the changes in Per2 and Clock. Concerning sleep homeostasis, KO mice accrued only half the extra REM sleep wild-type (WT) littermates obtained during recovery. Unexpectedly, KO mice were more active during lights-off which was accompanied by an acceleration of theta oscillations. Thus, CIRBP adjusts cortical clock gene expression after SD and expedites REM sleep recovery.

neuroscience↗