Sleep and circadian rhythms in α‐synucleinopathies—Perspectives for disease modification DOI Creative Commons
Dieter Kunz, Henrik Oster, Oliver Rawashdeh

et al.

Acta Physiologica, Journal Year: 2023, Volume and Issue: 238(1)

Published: March 23, 2023

Abstract The global north is facing an unprecedented rise in the prevalence of neurodegenerative diseases. increasing incidence Parkinson's disease being referred to as a pandemic. reason for enormous increase only partly understood. Lifestyle factors are known play role, but they alone cannot account surge. One factor that—although recognized important—has not been explored detail so far influence circadian rhythms. Sleep and rhythm disruption key neurodegeneration, their occurrence during early stages suggests causal role pathogenesis. Isolated rapid eye movement (REM) sleep behavior disorder (iRBD) has identified prodromal state α‐synucleinopathies, such disease, Lewy body dementia, multiple system atrophy offering window insights into development these Even though REM most pronounced, driven modulated by timing system, specific abnormalities have described iRBD. Novel experimental clinical approaches exploiting molecular circuitry underlying timekeeping hold promise disentangle some pathophysiologic mechanisms α‐synucleinopathies. In this review, we summarize current knowledge on disruptions α‐synucleinopathies with emphasis aspects therapeutic potentials. These might contribute our understanding pathogenesis diseases may allow interventions addressing disturbed at stage disease.

Language: Английский

Impaired Glymphatic and Meningeal Lymphatic Functions in Patients with Chronic Migraine DOI
Chia‐Hung Wu, Feng‐Chi Chang, Yen‐Feng Wang

et al.

Annals of Neurology, Journal Year: 2023, Volume and Issue: 95(3), P. 583 - 595

Published: Dec. 7, 2023

Objective This study was undertaken to investigate migraine glymphatic and meningeal lymphatic vessel (mLV) functions. Methods Migraine patients healthy controls (HCs) were prospectively recruited between 2020 2023. Diffusion tensor image analysis along the perivascular space (DTI‐ALPS) index for glymphatics dynamic contrast‐enhanced magnetic resonance imaging parameters (time peak [TTP]/enhancement integral [EI]/mean time enhance [MTE]) para‐superior sagittal (paraSSS)‐mLV or paratransverse sinus (paraTS)‐mLV in episodic (EM), chronic (CM), CM with without medication‐overuse headache (MOH) analyzed. DTI‐ALPS correlations clinical (migraine severity [numeric rating scale]/disability [Migraine Disability Assessment (MIDAS)]/bodily pain [Widespread Pain Index]/sleep quality [Pittsburgh Sleep Quality Index (PSQI)]) examined. Results In total, 175 subjects (112 + 63 HCs) investigated. values lower (median [interquartile range] = 0.64 [0.12]) than EM (0.71 [0.13], p 0.005) HCs [0.09], 0.004). MOH (0.63 [0.07]) had (0.73 [0.12], < 0.001). Furthermore, longer TTP (paraSSS‐mLV: 55.8 [12.9] vs 40.0 [7.6], 0.001; paraTS‐mLV: 51.2 [8.1] 44.0 [3.3], 0.002), EI 45.5 [42.0] 16.1 [9.2], 0.001), MTE 253.7 [6.7] 248.4 [13.8], 252.0 [6.2] 249.7 [1.2], 0.001) patients. The MIDAS ( 0.002) PSQI negatively correlated after Bonferroni corrections q 0.01). Interpretation patients, particularly those MOH, have dysfunctions, which are highly clinically relevant may implicate pathogenesis chronification. ANN NEUROL 2024;95:583–595

Language: Английский

Citations

32
Recent Advances in the Etiology and Treatment of Burning Mouth Syndrome DOI

A. Ritchie,

Jill M. Kramer

Journal of Dental Research, Journal Year: 2018, Volume and Issue: 97(11), P. 1193 - 1199

Published: June 18, 2018

Burning mouth syndrome (BMS) is a debilitating condition that has striking female predilection. Although the oral mucosa normal in appearance, patients with BMS experience burning most commonly localizes to lips and tongue. diagnosis of exclusion, all underlying pathoses associated allodynia must be ruled out prior rendering diagnosis. The etiopathogenesis remains poorly understood, thus patient management challenging. Data indicate systemic factors both contribute development persistence condition. Of particular interest, emerging work identifies structural functional deficits within nervous system may lead more mechanistic understanding pathology. In addition, several novel findings suggest circadian rhythm dysfunction previously unappreciated yet clinically significant driver disease. Circadian controls pain perception, mood, sleep plays key role regulation hypothalamic-pituitary-adrenal axis. Since these are altered BMS, this reflective dysfunction. While evidence-based treatment strategies for lacking, current approaches consist local medications, such as clonazepam, alpha lipoic acid, capsaicin, low-level laser therapy, gabapentin, amitriptylin. use cognitive behavioral therapy reported. This review provides an overview recent literature related etiology challenges facing researchers clinicians alike.

Language: Английский

Citations

78
Promoting endothelial cell affinity and antithrombogenicity of polytetrafluoroethylene (PTFE) by mussel-inspired modification and RGD/heparin grafting DOI
Hao‐Yang Mi, Xin Jing,

James A. Thomsom

et al.

Journal of Materials Chemistry B, Journal Year: 2018, Volume and Issue: 6(21), P. 3475 - 3485

Published: Jan. 1, 2018

Chemical modification using dopamine, polyethylenimine, RGD and heparin enabled simultaneous promotion of endothelial cell affinity antithrombogenicity polytetrafluoroethylene.

Language: Английский

Citations

65
Roles of clock genes in the pathogenesis of Parkinson's disease DOI
Anastasiia D. Shkodina, Shing Cheng Tan, Mohammad Mehedi Hasan

et al.

Ageing Research Reviews, Journal Year: 2021, Volume and Issue: 74, P. 101554 - 101554

Published: Dec. 30, 2021

Language: Английский

Citations

54
NADPH and Mitochondrial Quality Control as Targets for a Circadian-Based Fasting and Exercise Therapy for the Treatment of Parkinson’s Disease DOI Creative Commons
William M. Curtis, William A. Seeds, Mark P. Mattson

et al.

Cells, Journal Year: 2022, Volume and Issue: 11(15), P. 2416 - 2416

Published: Aug. 4, 2022

Dysfunctional mitochondrial quality control (MQC) is implicated in the pathogenesis of Parkinson’s disease (PD). The improper selection mitochondria for mitophagy increases reactive oxygen species (ROS) levels and lowers ATP levels. downstream effects include oxidative damage, failure to maintain proteostasis ion gradients, decreased NAD+ NADPH levels, resulting insufficient energy metabolism neurotransmitter synthesis. A ketosis-based metabolic therapy that (R)-3-hydroxybutyrate (BHB) may reverse dysfunctional MQC by partially replacing glucose as an source, stimulating mitophagy, decreasing inflammation. Fasting can potentially raise cytoplasmic increasing export ketone body-derived citrate flux through isocitrate dehydrogenase 1 (IDH1). essential cofactor nitric oxide synthase, synthesized diffuse into matrix react with electron transport chain-synthesized superoxide form peroxynitrite. Excessive peroxynitrite production cause opening permeability transition pore (mPTP) depolarize activate PINK1-dependent mitophagy. Both fasting exercise increase ketogenesis cellular NAD+/NADH ratio, both which are beneficial neuronal metabolism. In addition, engage adaptive stress response signaling pathways protect neurons against proteotoxic PD. Here, we discuss how intermittent from evening meal next-day lunch together morning exercise, when circadian most oxidized, NADP+/NADPH reduced, gene expression high, slow progression

Language: Английский

Citations

36
PEDOT/CNT Flexible MEAs Reveal New Insights into the Clock Gene's Role in Dopamine Dynamics DOI Creative Commons
Bingchen Wu, Elisa Castagnola, Colleen A. McClung

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(27)

Published: March 2, 2024

Substantial evidence has shown that the Circadian Locomotor Output Cycles Kaput (Clock) gene is a core transcription factor of circadian rhythms regulates dopamine (DA) synthesis. To shed light on mechanism this interaction, flexible multielectrode arrays (MEAs) are developed can measure both DA concentrations and electrophysiology chronically. The dual functionality enabled by conducting polymer PEDOT doped with acid-functionalized carbon nanotubes (CNT). PEDOT/CNT microelectrode coating maintained stable electrochemical impedance detection square wave voltammetry for 4 weeks in vitro. When implanted wild-type (WT) Clock mutation (MU) mice, MEAs measured tonic concentration extracellular neural activity high spatial temporal resolution weeks. A diurnal change WT observed, but not MU, higher basal stronger cocaine-induced increase MU. Meanwhile, striatal neuronal firing rate found to be positively correlated animal groups. These findings offer new insights into dynamics context rhythm regulation, chronically reliable performance measurement capability technology hold great potential broad range neuroscience research.

Language: Английский

Citations

7
Unraveling the Interplay of Dopamine, Carbon Monoxide, and Heme Oxygenase in Neuromodulation and Cognition DOI Creative Commons
Nicola Bauer, Dongning Liu,

TanPhat Nguyen

et al.

ACS Chemical Neuroscience, Journal Year: 2024, Volume and Issue: 15(3), P. 400 - 407

Published: Jan. 12, 2024

The dopaminergic system plays important roles in neuromodulation, including prominent complex neurological functions such as cognition, reward, motivation, and memory. Understandably, the highly nature of physiological means that their regulation is intertwined with other signaling pathways, has been demonstrated by numerous studies. Contrary to its public perception being poisonous at all concentrations, carbon monoxide (CO) produced endogenously from heme degradation oxygenase (HO) part process red blood cell turnover. Physiological concentrations CO can reach high micromolar ranges hemoglobin bound form. Low-dose shown therapeutic effects animal models, traumatic brain injury via engaging various hemoprotein targets. As such, HO–CO axis offer beneficial organ protection, anti-inflammation, neuroprotection, among many others. Further, a large number publications have interactions CO, HO, system. In this review, we critically examine experimental evidence holistic fashion context possible dopamine–HO–CO axis. We hope Perspective will stimulate additional investigations into molecular connectivity related open doors development novel therapeutics impact

Language: Английский

Citations

6
Sleep and Oxidative Stress: Current Perspectives on the Role of NRF2 DOI Creative Commons
Sergio Davinelli, Alessandro Medoro, Rosa Savino

et al.

Cellular and Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 44(1)

Published: June 25, 2024

Abstract Sleep is a fundamental conserved physiological state across evolution, suggesting vital biological functions that are yet to be fully clarified. However, our understanding of the neural and molecular basis sleep regulation has increased rapidly in recent years. Among various processes implicated controlling homeostasis, bidirectional relationship between oxidative stress recently emerged. One proposed function may mitigation both brain peripheral tissues, contributing clearance reactive species accumulate during wakefulness. Conversely, species, such as oxygen (ROS) nitrogen (RNS), at levels, act signaling agents regulate redox-sensitive transcriptional factors, enzymes, other effectors involved sleep. As primary sensor intracellular oxidation, transcription factor NRF2 emerging an indispensable component maintain cellular redox homeostasis Indeed, number studies have revealed association dysfunction most common conditions, including loss, obstructive apnea, circadian disturbances. This review examines evidence intricate link context sleep, highlights potential modulators alleviate Graphical A been shown, indicating play protective role against accumulation wakefulness deprivation. might also serve molecules influence mechanisms. Notably, changes, key regulator homeostasis.

Language: Английский

Citations

6
The role of dopamine in overcoming aversion with exercise DOI
Benjamin N. Greenwood

Brain Research, Journal Year: 2018, Volume and Issue: 1713, P. 102 - 108

Published: Aug. 29, 2018

Language: Английский

Citations

58
Embryonic and postnatal neurogenesis produce functionally distinct subclasses of dopaminergic neuron DOI Creative Commons
Elisa Galliano,

Eleonora Franzoni,

Marine Breton

et al.

eLife, Journal Year: 2018, Volume and Issue: 7

Published: April 19, 2018

Most neurogenesis in the mammalian brain is completed embryonically, but certain areas production of neurons continues throughout postnatal life. The functional properties mature postnatally generated often match those their embryonically produced counterparts. However, we show here that olfactory bulb (OB), embryonic and produce functionally distinct subpopulations dopaminergic (DA) neurons. We define two subclasses OB DA neuron by presence or absence a key subcellular specialisation: axon initial segment (AIS). Large AIS-positive axon-bearing are exclusively during early stages, leaving small anaxonic AIS-negative cells as only subtype via adult neurogenesis. These populations distinct: large more excitable, yet display weaker – for long-latency inhibitory events broadly tuned responses to odorant stimuli. Embryonic can therefore generate neuronal subclasses, placing important constraints on roles adult-born sensory processing.

Language: Английский

Citations

47