The Molecular Clock and Neurodegenerative Disease: A Stressful Time DOI Creative Commons

Bethany Carter,

Hannah Justin,

Danielle Gulick

et al.

Frontiers in Molecular Biosciences, Journal Year: 2021, Volume and Issue: 8

Published: March 26, 2021

Circadian rhythm dysfunction occurs in both common and rare neurodegenerative diseases. This manifests as sleep cycle mistiming, alterations body temperature rhythms, an increase symptomatology during the early evening hours known Sundown Syndrome. Disruption of circadian homeostasis has also been implicated etiology disease. Indeed, individuals exposed to a shifting schedule activity, such health care workers, are at higher risk. Thus, bidirectional relationship exists between system neurodegeneration. At heart this crosstalk is molecular clock, which functions regulate homeostasis. Over past decade, connection become focal point investigation clock offers attractive target combat disease pathogenesis dysfunction, pivotal role for neuroinflammation stress established. review summarizes contributions etiology, well mechanisms by diseases affect clock.

Language: Английский

Clearance systems in the brain—implications for Alzheimer disease DOI

Jenna M. Tarasoff-Conway,

Roxana O. Carare, Ricardo S. Osorio

et al.

Nature Reviews Neurology, Journal Year: 2015, Volume and Issue: 11(8), P. 457 - 470

Published: July 21, 2015

Language: Английский

Citations

1382
Glymphatic distribution of CSF-derived apoE into brain is isoform specific and suppressed during sleep deprivation DOI Creative Commons

Thiyagaragan M. Achariyar,

Baoman Li, Weiguo Peng

et al.

Molecular Neurodegeneration, Journal Year: 2016, Volume and Issue: 11(1)

Published: Dec. 1, 2016

Apolipoprotein E (apoE) is a major carrier of cholesterol and essential for synaptic plasticity. In brain, it's expressed by many cells but highly the choroid plexus predominant apolipoprotein in cerebrospinal fluid (CSF). The role apoE CSF unclear. Recently, glymphatic system was described as clearance whereby ISF (interstitial fluid) exchanged via peri-arterial space convective flow mediated aquaporin 4 (AQP4), water channel. We reasoned that this also serves to distribute molecules into brain. aim establish whether CSF, secreted plexus, distributed distribution pattern altered sleep deprivation.We used fluorescently labeled lipidated isoforms, lenti-apoE3 delivered immunohistochemistry map brain distribution, immunolabeled proteins Western blot analysis ELISA determine levels radiolabeled quantify inflow mice. Data were statistically analyzed using ANOVA or Student's t- test.We show transporting contributes delivery plexus/CSF-derived human neurons. CSF-delivered entered perivascular penetrating arteries flows radially around arteries, not veins, an isoform specific manner (apoE2 > apoE3 apoE4). Flow facilitated AQP4, characteristic feature system. ApoE3, lentivirus ependymal layer parenchymal cells, present which contains apoE, its from interstitium severely suppressed deprivation compared state.Thus, plexus/CSF provides additional source delivers it periarterial space. By implication, failure physiological may contribute isoform-specific disorders long term.

Language: Английский

Citations

205
The genetics of circadian rhythms, sleep and health DOI Creative Commons
Aarti Jagannath, Lewis Taylor,

Zeinab Wakaf

et al.

Human Molecular Genetics, Journal Year: 2017, Volume and Issue: 26(R2), P. R128 - R138

Published: July 11, 2017

Circadian rhythms are 24-h in physiology and behaviour generated by molecular clocks, which serve to coordinate internal time with the external world. The circadian system is a master regulator of nearly all its disruption has major consequences on health. Sleep rhythm (SCRD) ubiquitous feature today's 24/7 society, studies shift-workers have shown that SCRD can lead not only cognitive impairment, but also metabolic syndrome psychiatric illness including depression (1,2). Mouse models clock mutants recapitulate these deficits, implicating mechanistic causal links between disease pathophysiology (3-5). Importantly, treating reverses attenuates adverse health states animal (6,7), thus establishing as novel therapeutic target. Significantly, clock-controlled gene mutations recently been identified Genome-Wide Association Studies (GWAS) aetiology sleep, mental disorders. This review will focus upon genetics sleep

Language: Английский

Citations

203
The Links Between the Gut Microbiome, Aging, Modern Lifestyle and Alzheimer's Disease DOI Creative Commons
Sholpan Askarova, Bauyrzhan Umbayev, Abdul‐Razak Masoud

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2020, Volume and Issue: 10

Published: March 18, 2020

Gut microbiome is a community of microorganisms in the gastrointestinal tract. These bacteria have tremendous impact on human physiology healthy individuals and during an illness. Intestinal can influence one's health either directly by secreting biologically active substances such as vitamins, essential amino acids, lipids et cetera or indirectly modulating metabolic processes immune system. In recent years considerable information has been accumulated relationship between gut brain functions. Moreover, significant quantitative qualitative changes reported patients with Alzheimer's disease (AD). On other hand, highly sensitive to negative external lifestyle aspects, diet, sleep deprivation, circadian rhythm disturbance, chronic noise, sedentary behavior, which are also considered important risk factors for development sporadic AD. this regard, review focused analyzing links microbiome, modern lifestyle, aging disease.

Language: Английский

Citations

177
Dopamine: A Modulator of Circadian Rhythms in the Central Nervous System DOI Creative Commons

Kirill S. Korshunov,

Laura J. Blakemore,

Paul Q. Trombley

et al.

Frontiers in Cellular Neuroscience, Journal Year: 2017, Volume and Issue: 11

Published: April 2, 2017

Circadian rhythms are daily that regulate many biological processes - from gene transcription to behavior and a disruption of these can lead myriad health risks. entrained by light, their 24-h oscillation is maintained core molecular feedback loop composed canonical circadian ("clock") genes proteins. Different modulators help maintain the proper rhythmicity proteins, one emerging modulator dopamine. Dopamine has been shown have circadian-like activities in retina, olfactory bulb, striatum, midbrain, hypothalamus, where it regulates, regulated by, clock some areas. Thus, likely dopamine essential mechanisms five brain This review discusses studies showcase different dopaminergic may be involved with regulation areas' rhythms. Mechanisms include how receptor activity directly indirectly influence dopamine's interactions gap junctions neuronal excitability, release effects gated low- high-pass filters. Because neurons described this also inhibitory neurotransmitter GABA which influences protein expression we discuss articles explore contribute actions on Finally, understand loss function could rhythms, linking neurodegenerative disease Parkinson's Disease disruptions The purpose summarize growing evidence regulating either or indirectly, areas discussed here. An appreciation new treatments including pharmacological agents directed at alleviating various symptoms rhythm disruption.

Language: Английский

Citations

136
Sleep Disorders Associated With Alzheimer's Disease: A Perspective DOI Creative Commons
Anna Brzecka, Jerzy Leszek,

Ghulam Md Ashraf

et al.

Frontiers in Neuroscience, Journal Year: 2018, Volume and Issue: 12

Published: May 31, 2018

Sleep disturbances, as well sleep-wake rhythm are typical symptoms of Alzheimer's disease (AD) that may precede the other clinical signs and diagnosis this neurodegenerative disease. Here, we describe picture sleep disorders in AD relation between both cognitive impairment poor prognosis There difficulties based on questionnaires, polysomnography or actigraphy patients. Typical disturbances neurophysiological architecture course include deep paradoxical deprivation. Among occurring patients with AD, most frequent breathing – mainly obstructive apnea (OSA) syndrome restless legs syndrome/periodic movements' syndrome. influence circadian fluctuations concentrations amyloid-β interstitial brain fluid cerebrovascular related to glymphatic system production amyloid-β. is accumulating evidence suggesting disordered contributes decline development pathology. In mini-review, highlight discuss association AD.

Language: Английский

Citations

123
Circadian Regulation of Hippocampal-Dependent Memory: Circuits, Synapses, and Molecular Mechanisms DOI Creative Commons

Kaitlin H. Snider,

Kyle A. Sullivan, Karl Obrietan

et al.

Neural Plasticity, Journal Year: 2018, Volume and Issue: 2018, P. 1 - 13

Published: Jan. 1, 2018

Circadian modulation of learning and memory efficiency is an evolutionarily conserved phenomenon, occurring in organisms ranging from invertebrates to higher mammalian species, including humans. While the suprachiasmatic nucleus (SCN) hypothalamus functions as master pacemaker, recent evidence suggests that forebrain regions, hippocampus, exhibit oscillatory capacity. This finding, well work on cellular signaling events underlie memory, has opened promising new avenues investigation into precise cellular, molecular, circuit-based mechanisms by which clock timing impacts plasticity cognition. In this review, we examine complex molecular relationship between with a focus hippocampal-dependent tasks. We evaluate how dysregulation circadian timing, both at level SCN ancillary clocks, affects memory. Further, discuss experimentally validated intracellular pathways (e.g., ERK/MAPK GSK3 β ) potential formation. Finally, long-term potentiation (LTP), synaptic process critical establishment several forms regulated clock-gated processes.

Language: Английский

Citations

95
Interaction of melatonin and Bmal1 in the regulation of PI3K/AKT pathway components and cellular survival DOI Creative Commons
Mustafa Çağlar Beker, Berrak Çağlayan, Ahmet Burak Çağlayan

et al.

Scientific Reports, Journal Year: 2019, Volume and Issue: 9(1)

Published: Dec. 13, 2019

Abstract The circadian rhythm is driven by a master clock within the suprachiasmatic nucleus which regulates rhythmic secretion of melatonin. Bmal1 coordinates expression transcriptome and biological activities, involved in cell metabolism aging. However, role cellular- survival, signaling, its interaction with intracellular proteins, how melatonin largely unclear. Here we observed that increases both increase cellular survival after oxygen glucose deprivation (OGD) while inhibition resulted decreased without affecting neuroprotective effects By using planar surface immunoassay for PI3K/AKT signaling pathway components, revealed increased phosphorylation AKT, ERK-1/2, PDK1, mTOR, PTEN, GSK-3αβ, p70S6K. In contrast, these effect on molecules was not affected absence Bmal1. Besides, OGD vitro focal cerebral ischemia vivo . Our data demonstrate controls via plays critical roles activation kinases.

Language: Английский

Citations

91
Human circadian variations DOI Open Access
Nicholas W. Gentry, Liza H. Ashbrook, Ying‐Hui Fu

et al.

Journal of Clinical Investigation, Journal Year: 2021, Volume and Issue: 131(16)

Published: Aug. 15, 2021

Circadian rhythms, present in most phyla across life, are biological oscillations occurring on a daily cycle. Since the discovery of their molecular foundations model organisms, many inputs that modify this tightly controlled system humans have been identified. Polygenic variations and environmental factors influence each person's circadian rhythm, contributing to trait known as chronotype, which manifests degree morning or evening preference an individual. Despite normal variation much society operates "one size fits all" schedule can be difficult adjust to, especially for certain individuals whose endogenous phase is extremely advanced delayed. This public health concern, misalignment associated with number adverse outcomes. Additionally, modern technology (such electric lights computer, tablet, phone screens emit blue light) lifestyles shift irregular work schedules) disrupting consistency increasing people. Though medical lifestyle interventions alleviate some these issues, growing research variability sensitivity suggests broader social changes may necessary minimize impact health.

Language: Английский

Citations

84
Sleep and circadian rhythms in Parkinson’s disease and preclinical models DOI Creative Commons
Jeremy Hunt, Elizabeth J. Coulson, Rajendram V. Rajnarayanan

et al.

Molecular Neurodegeneration, Journal Year: 2022, Volume and Issue: 17(1)

Published: Jan. 9, 2022

The use of animals as models human physiology is, and has been for many years, an indispensable tool understanding the mechanisms disease. In Parkinson's disease, various mouse form cornerstone these investigations. Early were developed to reflect traditional histological features motor symptoms However, it is important that accurately encompass facets disease allow comprehensive mechanistic translational significance. Circadian rhythm sleep issues are tightly correlated often arise prior presentation typical deficits. It essential used understand dysfunctions in circadian rhythms sleep, both facilitate investigations into interplay between assist development rhythm-facing therapeutic treatments. This review describes extent which genetically- neurotoxically-induced murine abnormalities observed clinic.

Language: Английский

Citations

63