Sleep deprivation exacerbates microglial reactivity and Aβ deposition in a TREM2 -dependent manner in mice

Science Translational Medicine, Год журнала: 2023, Номер 15(693)

Опубликована: Апрель 26, 2023

Sleep loss is associated with cognitive decline in the aging population and a risk factor for Alzheimer’s disease (AD). Considering crucial role of immunomodulating genes such as that encoding triggering receptor expressed on myeloid cells type 2 (TREM2) removing pathogenic amyloid-β (Aβ) plaques regulating neurodegeneration brain, our aim was to investigate whether how sleep influences microglial function mice. We chronically sleep-deprived wild-type mice 5xFAD mouse model cerebral amyloidosis, expressing either humanized TREM2 common variant, loss-of-function R47H AD-associated or without expression. deprivation not only enhanced TREM2-dependent Aβ plaque deposition compared normal sleeping patterns but also induced reactivity independent presence parenchymal plaques. investigated lysosomal morphology using transmission electron microscopy found abnormalities particularly observed maturation impairments manner both microglia neurons, suggesting changes modified neuro-immune cross-talk. Unbiased transcriptome proteome profiling provided mechanistic insights into functional pathways triggered by were unique pathology converged metabolic dyshomeostasis. Our findings highlight directly affects reactivity, which required, altering ability cope energy demands prolonged wakefulness, leading further deposition, underlines importance modulation promising future therapeutic approach.

Язык: Английский

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Astrocytic modulation of neuronal signalling

Frontiers in Network Physiology, Год журнала: 2023, Номер 3

Опубликована: Июнь 1, 2023

Neuronal signalling is a key element in neuronal communication and essential for the proper functioning of CNS. Astrocytes, most prominent glia brain play role modulating at molecular, synaptic, cellular, network levels. Over past few decades, our knowledge about astrocytes their has evolved from considering them as merely glue that provides structural support to neurons, elements. Astrocytes can regulate activity neurons by controlling concentrations ions neurotransmitters extracellular milieu, well releasing chemicals gliotransmitters modulate activity. The aim this review summarise main processes through which are function. We will systematically distinguish between direct indirect pathways affect all Lastly, we summarize pathological conditions arise once these impaired focusing on neurodegeneration.

Язык: Английский

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Rescue of astrocyte activity by the calcium sensor STIM1 restores long-term synaptic plasticity in female mice modelling Alzheimer’s disease

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Март 22, 2023

Calcium dynamics in astrocytes represent a fundamental signal that through gliotransmitter release regulates synaptic plasticity and behaviour. Here we present longitudinal study the PS2APP mouse model of Alzheimer's disease (AD) linking astrocyte Ca2+ hypoactivity to memory loss. At onset plaque deposition, somatosensory cortical AD female mice exhibit drastic reduction signaling, closely associated with decreased endoplasmic reticulum concentration reduced expression sensor STIM1. In parallel, astrocyte-dependent long-term declines circuitry, anticipating specific tactile Notably, show both signaling are fully recovered by selective STIM1 overexpression astrocytes. Our data unveil neocortical as functional hallmark early stages indicate astrocytic target rescue deficits.

Язык: Английский

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The stress of losing sleep: Sex-specific neurobiological outcomes

Neurobiology of Stress, Год журнала: 2023, Номер 24, С. 100543 - 100543

Опубликована: Май 1, 2023

Sleep is a vital and evolutionarily conserved process, critical to daily functioning homeostatic balance. Losing sleep inherently stressful leads numerous detrimental physiological outcomes. Despite disturbances affecting everyone, women female rodents are often excluded or underrepresented in clinical pre-clinical studies. Advancing our understanding of the role biological sex responses loss stands greatly improve ability understand treat health consequences insufficient sleep. As such, this review discusses differences response deprivation, with focus on sympathetic nervous system stress activation hypothalamic-pituitary-adrenal (HPA) axis. We several stress-related loss, including inflammation, learning memory deficits, mood related changes. Focusing women's health, we discuss effects deprivation during peripartum period. In closing, present neurobiological mechanisms, contribution hormones, orexins, circadian timing systems, astrocytic neuromodulation, that may underlie potential responses.

Язык: Английский

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Astroglial functions

Neuroglia, Год журнала: 2023, Номер unknown, С. 199 - 294

Опубликована: Янв. 1, 2023

Astroglial cells are fundamental for the most basic functions of central nervous system, which define its development, maintenance, survival and operation. Astroglia key element brain barriers, production turnover cerebrospinal fluid, ionostasis extracellular space. Astrocytes maintain function glymphatic system responsible from removal cellular waste. an indispensable part synaptic networks, controlling synaptogenesis, maintenance elimination, through astroglial cradle. Finally, astrocytic morphological functional plasticity critical elements plastic remodelling neuronal ensembles, this being learning, memory behaviour.

Язык: Английский

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Sleep and Immune Health: How Dogs, Goats and ‘Factor S’ Shaped a Field: Festschrift in Honor of JM Krueger’s Research

Neurobiology of Sleep and Circadian Rhythms, Год журнала: 2025, Номер unknown, С. 100118 - 100118

Опубликована: Апрель 1, 2025

Язык: Английский

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Astrocytes: new evidence, new models, new roles

Biophysical Reviews, Год журнала: 2023, Номер 15(5), С. 1303 - 1333

Опубликована: Окт. 1, 2023

Язык: Английский

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Mechanisms of Activation of Brain’s Drainage during Sleep: The Nightlife of Astrocytes

Cells, Год журнала: 2023, Номер 12(22), С. 2667 - 2667

Опубликована: Ноя. 20, 2023

The study of functions, mechanisms generation, and pathways movement cerebral fluids has a long history, but the last decade been especially productive. proposed glymphatic hypothesis, which suggests mechanism brain waste removal system (BWRS), caused an active discussion on both criticism some perspectives our intensive new experimental facts. It was found that intensity metabolite clearance changes significantly during transition between sleep wakefulness. Interestingly, at cellular level, number aspects this problem have focused on, such as astrocytes-glial cells, which, over past two decades, recognized equal partners neurons perform many important functions. In particular, role assigned to astrocytes within framework hypothesis. review, we return "astrocytocentric" view BWRS function explanation its activation from viewpoint findings decade. Our main conclusion is BWRS's action may be analyzed systemic (whole-brain) local (cellular) level. level means here neuro-glial-vascular unit can also regarded smallest functional sleep, therefore, BWRS.

Язык: Английский

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A Global Transcriptional Atlas of the Effect of Acute Sleep Deprivation in the Mouse Frontal Cortex

iScience, Год журнала: 2024, Номер 27(9), С. 110752 - 110752

Опубликована: Авг. 17, 2024

Sleep deprivation (SD) has negative effects on brain and body function. problems are prevalent in a variety of disorders, including neurodevelopmental psychiatric conditions. Thus, understanding the molecular consequences SD is fundamental importance biology. In this study, we present first simultaneous bulk single-nuclear RNA sequencing characterization male mouse frontal cortex. We show that predominantly affects glutamatergic neurons, specifically layers 4 5, produces isoform switching over 1500 genes, particularly those involved splicing binding. At both global cell-type specific level, large repressive effect transcription, downregulating thousands genes transcripts. As resource provide extensive characterizations cell-types, transcripts, pathways affected by SD. also publicly available tutorials aimed at allowing readers adapt analyses performed study to their own datasets.

Язык: Английский

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Glia: The Cellular Glue that binds Circadian Rhythms and Sleep

SLEEP, Год журнала: 2025, Номер unknown

Опубликована: Янв. 15, 2025

Glia are increasingly appreciated as serving an important function in the control of sleep and circadian rhythms. Glial cells Drosophila mammals regulate daily rhythms locomotor activity well homeostatic rebound following deprivation. In addition, they contribute to proposed functions sleep, with different mapping varied glial subtypes. Here, we discuss recent findings rodent models establishing a role glia or regulation synaptic plasticity, brain metabolism, removal cellular debris immune challenges. These underscore relevance for benefits attributed have implications understanding neurobiological mechanisms underlying associated disorders.

Язык: Английский

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