Importance of the locus coeruleus-norepinephrine system in sleep-wake regulation: Implications for aging and Alzheimer's disease

Sleep Medicine Reviews, Journal Year: 2022, Volume and Issue: 62, P. 101592 - 101592

Published: Jan. 21, 2022

Five decades ago, seminal studies positioned the brainstem locus coeruleus (LC) norepinephrine (NE) system as a key substrate for regulation of wakefulness and sleep, this picture has recently been elaborated thanks to methodological advances in precise investigation experimental modulation LC structure functions. This review presents discusses findings that support major role LC-NE at different levels sleep-wake organization, ranging from its involvement overall architecture cycle associations with sleep microstructure, while accounting intricate neuroanatomy surrounding LC. Given particular position held by being intersection dysregulation initial pathophysiological processes Alzheimer's disease (AD), we conclude examining emerging opportunities investigate mediated relationships between alteration AD human aging. We further propose several research perspectives could promising target identification at-risk individuals preclinical stages AD, development novel preventive interventions.

Language: Английский

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Neurobiology and systems biology of stress resilience

Physiological Reviews, Journal Year: 2024, Volume and Issue: 104(3), P. 1205 - 1263

Published: March 14, 2024

Stress resilience is the phenomenon that some people maintain their mental health despite exposure to adversity or show only temporary impairments followed by quick recovery. Resilience research attempts unravel factors and mechanisms make possible harness its insights for development of preventative interventions in individuals at risk acquiring stress-related dysfunctions. Biological has been lagging behind psychological social sciences but seen a massive surge recent years. At same time, progress this field hampered methodological challenges related finding suitable operationalizations study designs, replicating findings, modeling animals. We embed review behavioral, neuroimaging, neurobiological, systems biological findings adults critical methods discussion. find preliminary evidence hippocampus-based pattern separation prefrontal-based cognitive control functions protect against pathological fears aftermath singular, event-type stressors [as found fear-related disorders, including simpler forms posttraumatic stress disorder (PTSD)] facilitating perception safety. Reward system-based pursuit savoring positive reinforcers appear more generalized dysfunctions anxious-depressive spectrum resulting from severe longer-lasting (as depression, comorbid anxiety, PTSD). Links between preserved functioning these neural under neuroplasticity, immunoregulation, gut microbiome composition, integrity barrier blood-brain are beginning emerge. On basis, avenues pointed out.

Language: Английский

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Neurobehavioral meaning of pupil size

Neuron, Journal Year: 2024, Volume and Issue: 112(20), P. 3381 - 3395

Published: June 25, 2024

Pupil size is a widely used metric of brain state. It one the few signals originating from that can be readily monitored with low-cost devices in basic science, clinical, and home settings. is, therefore, important to investigate generate well-defined theories related specific interpretations this metric. What exactly does it tell us about brain? Pupils constrict response light dilate during darkness, but also controls pupil irrespective luminosity. fluctuations resulting ongoing "brain states" are as arousal, what pupil-linked arousal how should interpreted neural, cognitive, computational terms? Here, we discuss some recent findings these issues. We identify open questions propose answer them through combination tasks, neurocomputational models, neurophysiological probing interconnected loops causes consequences size.

Language: Английский

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Neural contributors to trauma resilience: a review of longitudinal neuroimaging studies

Translational Psychiatry, Journal Year: 2021, Volume and Issue: 11(1)

Published: Oct. 5, 2021

Abstract Resilience in the face of major life stressors is changeable over time and with experience. Accordingly, differing sets neurobiological factors may contribute to an adaptive stress response before, during, after stressor. Longitudinal studies are therefore particularly effective answering questions about determinants resilience. Here we provide overview rapidly-growing body longitudinal neuroimaging research on Despite lingering gaps limitations, these beginning reveal individual differences neural circuit structure function that appear protective against emergence future psychopathology following a outline model resilience trauma. Specifically, pre-trauma biomarkers show ability modulate activity within threat salience networks predicts fewer stress-related symptoms. In contrast, early post-trauma subsequent or recovery more complex pattern, spanning number circuits including attention cognitive control as well primary sensory cortices. This novel synthesis suggests be scaffolded by stable processing cues, further buttressed adaptations stressor encompass multiple mechanisms circuits. More resources supporting this work will inform targets timing mechanistic resilience-boosting interventions.

Language: Английский

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A Liquid Interfacial SERS Platform on a Nanoparticle Array Stabilized by Rigid Probes for the Quantification of Norepinephrine in Rat Brain Microdialysates

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(21)

Published: March 3, 2022

Abstract For the reliable determination of trace chemicals in brain, we created a SERS platform based on functionalized AuNPs array formed at liquid/liquid interface uniform fashion over large substrate area through ternary regulations for real‐time quantification norepinephrine (NE). The rigid molecule, 4‐(thiophen‐3‐ylethynyl)‐benzaldehyde (RP1) was designed and co‐assembled with 4‐mercaptophenylboronic acid (MPBA) to chemically define NE via dual recognition. Meanwhile, structure assembly RP1 MPBA efficiently fixed interparticle gap, guaranteeing reproducible analysis. Furthermore, Raman peak C≡C group silent region taken as response element further improve accuracy. Combined microdialysis, this developed in‐the‐field testing rat brain microdialysates following anxiety.

Language: Английский

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The role of the locus coeruleus in shaping adaptive cortical melodies

Trends in Cognitive Sciences, Journal Year: 2022, Volume and Issue: 26(6), P. 527 - 538

Published: April 22, 2022

Language: Английский

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Priorities for research on neuromodulatory subcortical systems in Alzheimer's disease: Position paper from the NSS PIA of ISTAART

Alzheimer s & Dementia, Journal Year: 2023, Volume and Issue: 19(5), P. 2182 - 2196

Published: Jan. 15, 2023

Abstract The neuromodulatory subcortical system (NSS) nuclei are critical hubs for survival, hedonic tone, and homeostasis. Tau‐associated NSS degeneration occurs early in Alzheimer's disease (AD) pathogenesis, long before the emergence of pathognomonic memory dysfunction cortical lesions. Accumulating evidence supports role behavioral neuropsychiatric manifestations featured AD. Experimental studies even suggest that AD‐associated drives brain neuroinflammatory status contributes to progression, including exacerbation Given important pathophysiologic etiologic roles involve AD stages, there is an urgent need expand our understanding mechanisms underlying vulnerability more precisely detail clinical progression changes Here, Professional Interest Area International Society Advance Research Treatment highlights knowledge gaps about within provides recommendations priorities specific research, biomarker development, modeling, intervention. Highlights Neuromodulatory degenerate pathological stages. pathophysiology exacerbated by degeneration. symptoms dementia. Biomarkers integrity would be value‐creating dementia care. present strategic prospects disease‐modifying therapies.

Language: Английский

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Phasic, Event-Related Transcutaneous Auricular Vagus Nerve Stimulation Modifies Behavioral, Pupillary, and Low-Frequency Oscillatory Power Responses

Journal of Neuroscience, Journal Year: 2023, Volume and Issue: 43(36), P. 6306 - 6319

Published: Aug. 17, 2023

Transcutaneous auricular vagus nerve stimulation (taVNS) has been proposed to activate the locus ceruleus-noradrenaline (LC-NA) system. However, previous studies failed find consistent modulatory effects of taVNS on LC-NA biomarkers. Previous suggest that phasic may be capable modulating biomarkers such as pupil dilation and alpha oscillations. it is unclear whether these extend beyond pure sensory vagal responses. Critically, potential pupillary light reflex an additional biomarker not explored so far. Here, we applied active sham in 29 subjects (16 female, 13 male) while they performed emotional Stroop task (EST) a passive (PLRT). We recorded size brain activity dynamics using combined Magnetoencephalography (MEG) pupillometry design. Our results show significantly increased performance during EST. During PLRT, reduced delayed constriction. In MEG, frontal-midline theta power EST, whereas occipital was both EST PLRT. findings provide evidence systematically modulates behavioral, pupillary, electrophysiological parameters cognitive processing. Moreover, demonstrate for first time can used simple effective proxy efficacy. These have important implications development noninvasive neuromodulation interventions various clinical applications.SIGNIFICANCE STATEMENT gained increasing attention technique widely nonclinical research. Nevertheless, exact mechanism action yet fully understood. By assessing physiology behavior response conflict healthy humans, successful application phasic, improve control modulate markers noradrenergic Understanding mechanisms could optimize future applications lead better treatments mental disorders associated with dysfunction. addition, present new taVNS-sensitive measure representing easy-to-use studies.

Language: Английский

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Mindfulness-Based Stress Reduction Increases Mental Wellbeing and Emotion Regulation During the First Wave of the COVID-19 Pandemic: A Synchronous Online Intervention Study

Frontiers in Psychology, Journal Year: 2021, Volume and Issue: 12

Published: Nov. 11, 2021

The COVID-19 pandemic imposed extreme living conditions of social distancing, which triggered negative mental health problems and created challenges in seeking support. Mindfulness-based interventions (MBIs) have been found to enhance wellbeing by reducing stress anxiety improving emotion regulation. Preliminary evidence suggests that online, synchronous MBIs may produce beneficial effects similar face-to-face programs. However, the effectiveness such online-MBIs support highly stressful times, as a global pandemic, requires further study. To this end, we investigated effect an online 8-week Mindfulness-Based Stress Reduction (MBSR) program on aspects during first wave pandemic. Participants ( N =92) who expressed interest discounted online-MBSR programs were recruited for division into experimental control groups was based actual enrollment courses. Those enrolled assigned condition those decided not enroll served controls. assessed pre-intervention, post-intervention, 1-month post-intervention levels mindfulness, perceived stress, anxiety, regulation, intolerance uncertainty. Differences between tested using general linear mixed model (GLMM) Individual Growth Curve Models (IGCM) intent treat analysis. findings indicated that, relative group, MBSR improved mindfulness abilities p <0.001), decreased <0.001) increased regulation <0.001). These persist 1 month after end program, despite governmental public-health restrictions due at time. ability tolerate uncertainty, central characteristic be affected program. A mediation analysis revealed intervention improvement partially mediated Overall, provide positive feasibility individuals from population through challenging

Language: Английский

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Consequences of Hyperphosphorylated Tau in the Locus Coeruleus on Behavior and Cognition in a Rat Model of Alzheimer’s Disease

Journal of Alzheimer s Disease, Journal Year: 2022, Volume and Issue: 86(3), P. 1037 - 1059

Published: Feb. 11, 2022

Background: The locus coeruleus (LC) is one of the earliest brain regions to accumulate hyperphosphorylated tau, but a lack animal models that recapitulate this pathology has hampered our understanding its contributions Alzheimer’s disease (AD) pathophysiology. Objective: We previously reported TgF344-AD rats, which overexpress mutant human amyloid precursor protein and presenilin-1, early endogenous tau in LC. Here, we used rats wild-type (WT) virus interrogate effects rat LC on AD-related neuropathology behavior. Methods: Two-month-old WT received bilateral infusions full-length or mCherry control driven by noradrenergic-specific PRSx8 promoter. Rats were subsequently assessed at 6 12 months for arousal (sleep latency), anxiety-like behavior (open field, elevated plus maze, novelty-suppressed feeding), passive coping (forced swim task), learning memory (Morris water maze fear conditioning). Hippocampal microglia, astrocyte, AD evaluated using immunohistochemistry. Results: In general, age more pronounced than genotype treatment; older displayed greater hippocampal pathology, took longer fall asleep, had reduced locomotor activity, floated more, impaired cognition compared younger animals. showed increased memory. negligible influence most measures. Conclusion: Effects AD-like behavioral symptoms subtle. Further investigation different forms warranted.

Language: Английский

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