Dataset Information

The sleep-wake cycle regulates brain interstitial fluid tau in mice and CSF tau in humans.

ABSTRACT: The sleep-wake cycle regulates interstitial fluid (ISF) and cerebrospinal fluid (CSF) levels of ?-amyloid (A?) that accumulates in Alzheimer's disease (AD). Furthermore, chronic sleep deprivation (SD) increases A? plaques. However, tau, not A?, accumulation appears to drive AD neurodegeneration. We tested whether ISF/CSF tau and tau seeding and spreading were influenced by the sleep-wake cycle and SD. Mouse ISF tau was increased ~90% during normal wakefulness versus sleep and ~100% during SD. Human CSF tau also increased more than 50% during SD. In a tau seeding-and-spreading model, chronic SD increased tau pathology spreading. Chemogenetically driven wakefulness in mice also significantly increased both ISF A? and tau. Thus, the sleep-wake cycle regulates ISF tau, and SD increases ISF and CSF tau as well as tau pathology spreading.

SUBMITTER: Holth JK

PROVIDER: S-EPMC6410369 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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The sleep-wake cycle regulates brain interstitial fluid tau in mice and CSF tau in humans.

Holth Jerrah K JK Fritschi Sarah K SK Wang Chanung C Pedersen Nigel P NP Cirrito John R JR Mahan Thomas E TE Finn Mary Beth MB Manis Melissa M Geerling Joel C JC Fuller Patrick M PM Lucey Brendan P BP Holtzman David M DM

Science (New York, N.Y.) 20190124 6429

The sleep-wake cycle regulates interstitial fluid (ISF) and cerebrospinal fluid (CSF) levels of β-amyloid (Aβ) that accumulates in Alzheimer's disease (AD). Furthermore, chronic sleep deprivation (SD) increases Aβ plaques. However, tau, not Aβ, accumulation appears to drive AD neurodegeneration. We tested whether ISF/CSF tau and tau seeding and spreading were influenced by the sleep-wake cycle and SD. Mouse ISF tau was increased ~90% during normal wakefulness versus sleep and ~100% during SD. Hu ...[more]

PMID: 30679382

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Project description:BackgroundScale-invariant neuronal avalanches have been observed in cell cultures and slices as well as anesthetized and awake brains, suggesting that the brain operates near criticality, i.e. within a narrow margin between avalanche propagation and extinction. In theory, criticality provides many desirable features for the behaving brain, optimizing computational capabilities, information transmission, sensitivity to sensory stimuli and size of memory repertoires. However, a thorough characterization of neuronal avalanches in freely-behaving (FB) animals is still missing, thus raising doubts about their relevance for brain function.Methodology/principal findingsTo address this issue, we employed chronically implanted multielectrode arrays (MEA) to record avalanches of action potentials (spikes) from the cerebral cortex and hippocampus of 14 rats, as they spontaneously traversed the wake-sleep cycle, explored novel objects or were subjected to anesthesia (AN). We then modeled spike avalanches to evaluate the impact of sparse MEA sampling on their statistics. We found that the size distribution of spike avalanches are well fit by lognormal distributions in FB animals, and by truncated power laws in the AN group. FB data surrogation markedly decreases the tail of the distribution, i.e. spike shuffling destroys the largest avalanches. The FB data are also characterized by multiple key features compatible with criticality in the temporal domain, such as 1/f spectra and long-term correlations as measured by detrended fluctuation analysis. These signatures are very stable across waking, slow-wave sleep and rapid-eye-movement sleep, but collapse during anesthesia. Likewise, waiting time distributions obey a single scaling function during all natural behavioral states, but not during anesthesia. Results are equivalent for neuronal ensembles recorded from visual and tactile areas of the cerebral cortex, as well as the hippocampus.Conclusions/significanceAltogether, the data provide a comprehensive link between behavior and brain criticality, revealing a unique scale-invariant regime of spike avalanches across all major behaviors.

Dataset Information

The sleep-wake cycle regulates brain interstitial fluid tau in mice and CSF tau in humans.

Publications

The sleep-wake cycle regulates brain interstitial fluid tau in mice and CSF tau in humans.

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