Neuromodulatory subcortical nucleus integrity is associated with white matter microstructure, tauopathy and APOE status

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: June 3, 2024

Abstract The neuromodulatory subcortical nuclei within the isodendritic core (IdC) are earliest sites of tauopathy in Alzheimer’s disease (AD). They project broadly throughout brain’s white matter. We investigated relationship between IdC microstructure and whole-brain matter to better understand early neuropathological changes AD. Using multiparametric quantitative magnetic resonance imaging we observed two covariance patterns 133 cognitively unimpaired older adults (age 67.9 ± 5.3 years) with familial risk for integrity related 1) neurite density, 2) orientation dispersion tracts known be affected Pattern 2 was associated CSF concentration phosphorylated-tau, indicating AD specificity. Apolipoprotein-E4 carriers expressed both more strongly than non-carriers. variation is reflected matter, particularly AD-affected tracts, highlighting an mechanism pathological development.

Language: Английский

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Wide-spread brain activation and reduced CSF flow during avian REM sleep

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: June 5, 2023

Abstract Mammalian sleep has been implicated in maintaining a healthy extracellular environment the brain. During wakefulness, neuronal activity leads to accumulation of toxic proteins, which glymphatic system is thought clear by flushing cerebral spinal fluid (CSF) through In mice, this process occurs during non-rapid eye movement (NREM) sleep. humans, ventricular CSF flow also shown increase NREM sleep, as visualized using functional magnetic resonance imaging (fMRI). The link between and not studied birds before. Using fMRI naturally sleeping pigeons, we show that REM paradoxical state with wake-like brain activity, accompanied activation regions involved processing visual information, including optic flight. We further demonstrate increases relative but drops sharply Consequently, functions linked might come at expense waste clearance

Language: Английский

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Risk of neurodegenerative diseases in patients with sleep disorders: A nationwide population-based case-control study

Sleep Medicine, Journal Year: 2023, Volume and Issue: 107, P. 289 - 299

Published: May 19, 2023

Language: Английский

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Higher order diffusion imaging as a putative index of human sleep-related microstructural changes and glymphatic clearance

NeuroImage, Journal Year: 2023, Volume and Issue: 274, P. 120124 - 120124

Published: April 20, 2023

The brain has a unique macroscopic waste clearance system, termed the glymphatic system which utilises perivascular tunnels surrounded by astroglia to promote cerebrospinal-interstitial fluid exchange. Rodent studies have demonstrated marked increase in during sleep been linked sleep-induced expansion of extracellular space and concomitant reduction intracellular volume. However, despite being implicated pathophysiology multiple human neurodegenerative disorders, non-invasive techniques for imaging humans are currently limited. Here we acquired multi-shell diffusion weighted MRI (dwMRI) twenty-one healthy young participants (6 female, 22.3 ± 3.2 years) each scanned twice, once wakefulness induced combination one night deprivation 10 mg hypnotic zolpidem 30 min before scanning. To capture hypothesised sleep-associated changes intra/extracellular space, dwMRI were analysed using higher order modelling with prediction that increases interstitial (extracellular) volume would result decrease kurtosis, particularly areas associated slow wave generation at onset sleep. In line our hypothesis, observed global kurtosis (t15=2.82, p = 0.006) as well regional reductions early default mode network highly metabolically active wakefulness. Analysis higher-order representation (MAP-MRI) further indicated within domain rather than membrane permeability likely underpin kurtosis. These findings identify potential new method extend rodent suggest is also an humans.

Language: Английский

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Noradrenergic neuromodulation in ageing and disease

Neuroscience & Biobehavioral Reviews, Journal Year: 2023, Volume and Issue: 152, P. 105311 - 105311

Published: July 10, 2023

The locus coeruleus (LC) is a small brainstem structure located in the lower pons and main source of noradrenaline (NA) brain. Via its phasic tonic firing, it modulates cognition autonomic functions involved brain's immune response. extent degeneration to LC healthy ageing remains unclear, however, noradrenergic dysfunction may contribute pathogenesis Alzheimer's (AD) Parkinson's disease (PD). Despite their differences progression at later stages, early involvement lead comparable behavioural symptoms such as preclinical sleep problems neuropsychiatric result AD PD pathology. In this review, we draw attention mechanisms that underlie ageing, PD. We aim motivate future research investigate how system play pivotal role which also be relevant other neurodegenerative diseases.

Language: Английский

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Locus coeruleus activity while awake is associated with REM sleep quality in older individuals

JCI Insight, Journal Year: 2023, Volume and Issue: 8(20)

Published: Sept. 12, 2023

BACKGROUNDThe locus coeruleus (LC) is the primary source of norepinephrine in brain and regulates arousal sleep. Animal research shows that it plays important roles transition between sleep wakefulness, slow wave rapid eye movement (REMS). It unclear, however, whether activity LC predicts variability humans.METHODSWe used 7-Tesla functional MRI, electroencephalography (EEG), a questionnaire to test during wakefulness was associated with quality 33 healthy younger (~22 years old; 28 women, 5 men) 19 older (~61 14 individuals.RESULTSWe found that, but not participants, higher activity, as probed an auditory attentional task, worse subjective lower power over EEG theta band REMS. The results remained robust even when accounting for age-related changes integrity LC.CONCLUSIONThese findings suggest correlates perception essential oscillatory mode REMS, we may be target treatment sleep- diseases.FUNDINGThis work supported by Fonds National de la Recherche Scientifique (FRS-FNRS, T.0242.19 & J. 0222.20), Action Concertée - Fédération Wallonie-Bruxelles (ARC SLEEPDEM 17/27-09), Fondation Alzheimer (SAO-FRA 2019/0025), ULiège, European Regional Development Fund (Radiomed Biomed-Hub).

Language: Английский

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Locus Coeruleus-Norepinephrine System: Spheres of Influence and Contribution to the Development of Neurodegenerative Diseases

Frontiers in Bioscience-Landmark, Journal Year: 2024, Volume and Issue: 29(3)

Published: March 20, 2024

Locus coeruleus is a small bilateral nucleus in the brainstem. It main source of norepinephrine (noradrenaline) throughout central nervous system (about 70% all system), and, as shown numerous studies, it involved regulating significant number functions. The detailed study functions Coeruleus (LC) and its significance human life became possible only after development histofluorescence methods for monoamines 1960s. widespread locus coeruleus-norepinephrine (LC-NE) projection regulates entire modulates sensory processing, motor behavior, arousal, cognitive processes. Damage to LC associated decrease levels are wide range clinical conditions pathological Although much about anatomy physiology currently known, ultimate role regulation control sleep-wake cycle, stress response, (such Alzheimer’s disease, dementia, depression, suicidal chronic traumatic encephalopathy, Parkinson’s disease) not fully understood. Non-invasive visualization can be used differential diagnosis, determining stage predicting course. Studying dysfunction LC-norepinephrine system, pathogenesis various neurological diseases, may ultimately form basis new treatment based on pharmacological elevation levels. In this review, we will attempt highlight key points regarding structure function Coeruleus, well outline directions prospects study.

Language: Английский

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Selective Enhancement of REM Sleep in Male Rats through Activation of Melatonin MT₁Receptors Located in the Locus Ceruleus Norepinephrine Neurons

Journal of Neuroscience, Journal Year: 2024, Volume and Issue: 44(29), P. e0914232024 - e0914232024

Published: May 14, 2024

Sleep disorders affect millions of people around the world and have a high comorbidity with psychiatric disorders. While current hypnotics mostly increase non-rapid eye movement sleep (NREMS), drugs acting selectively on enhancing rapid (REMS) are lacking. This polysomnographic study in male rats showed that first-in-class selective melatonin MT 1 receptor partial agonist UCM871 increases duration REMS without affecting NREMS. The REMS-promoting effects occurred by inhibiting, dose–response manner, firing activity locus ceruleus (LC) norepinephrine (NE) neurons, which express receptors. inhibition LC-NE neuronal were abolished pharmacological antagonism an adeno-associated viral (AAV) vector, knocked down receptors neurons. In conclusion, agonism inhibits neurons triggers REMS, thus representing novel mechanism target for and/or associated impairments.

Language: Английский

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Prolactin in sleep and EEG regulation: new mechanisms and sleep-related brain targets complement classical data

Neuroscience & Biobehavioral Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 106000 - 106000

Published: Jan. 1, 2025

The role of prolactin in sleep regulation has been the subject extensive research over past 50 years, resulting identification multiple, disparate functions for hormone. Prolactin demonstrated a characteristic circadian release pattern with elevation during dark and diminution light. High levels were linked to non-rapid eye movement electroencephalogram delta activity humans. Conversely, hyperprolactinemia showed strong correlation REM rodent studies. may be implicated alterations female patterns observed reproductive cycle, it play enhancement following stress sleep-related immunological processes. In conclusion, appears have sleep-promoting role, particularly phase. However, does not appear central coherent regulation, as some neuropeptides such orexin. its principal function facilitate situational, yet adaptive, changes response challenging physiological phases, those associated stress, challenges, or cycle. Neuronal substrates prolactin-mediated effects remain unknown; however, recent studies provide insights into potential sites these effects.

Language: Английский

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Noradrenaline and Acetylcholine shape Functional Connectivity organization of NREM substages: an empirical and simulation study

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 6, 2025

Abstract Sleep onset is characterized by a departure from arousal, and can be separated into well-differentiated stages: NREM (which encompasses three substages: N1, N2 N3) REM (Rapid Eye Movement). Awake brain dynamics are maintained various wake-promoting mechanisms, particularly the neuromodulators Acetylcholine (ACh) Noradrenaline (NA), whose levels naturally decrease during transition to sleep. The combined influence of these neurotransmitters on connectivity sleep remains unclear, as previous models have examined them mostly in isolation or only deep In this study, we employ Whole Brain model investigate how changes neurochemistry sleep, specifically involving ACh NA, affect Functional Connectivity (FC) brain. Using Wilson-Cowan whole informed an empirical connectome heterogeneous receptivity map neuromodulators, explore dynamics. Initial FC analysis reveals distinct changes: Locus Coeruleus (LC) with cortex N3, Basal Forebrain (BF) N3. Additionally, compared Wakefulness (W), there more integrated state N1 segregated We adjust coupling input-output slope for based BF LC priors, show that region-specific neurotransmitter distribution key explaining their effects FC. This work enhances our understanding neurotransmitters’ roles modulating stages significant contribution transitions between different states consciousness, both health disease.

Language: Английский

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