Molecular Mechanisms of Neuroinflammation in ME/CFS and Long COVID to Sustain Disease and Promote Relapses

Frontiers in Neurology, Journal Year: 2022, Volume and Issue: 13

Published: May 25, 2022

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a disease now well-documented as having arisen commonly from viral infection, but also other external stressors, like exposure to agricultural chemicals, types of surgery, or severe stress events. Research has shown these events produce systemic molecular inflammatory response and chronic immune activation dysregulation. What been more difficult establish the hierarchy physiological responses that give rise myriad symptoms ME/CFS patients experience, why they do not resolve are generally life-long. The severity frequently fluctuates through relapse recovery periods, with brain-centered neuroinflammation, loss homeostatic control, "brain fog" affecting cognitive ability, lack refreshing sleep, poor even small stresses. How brain effects develop initiating effector, whether virus cause, poorly understood what our paper aims address. We propose hypothesis following initial stressor event, subsequent pathology moves via neurovascular pathways dysfunctional blood-brain barrier (BBB), resulting in neuroinflammation leading sustained illness cycles. Signaling recognized back body physiology likely part process by which cycle peripheral system healing does occur. By contrast, Long COVID (Post-COVID-19 condition) very recent ME/CFS-like arising single pandemic virus, SARS-CoV-2. believe ongoing similar mechanisms involving some unique signaling, SARS-CoV-2 infection. fact there both diseases, despite diversity nature supports concept CNS component common both.

Language: Английский

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Overexpression of Sirt6 ameliorates sleep deprivation induced-cognitive impairment by modulating glutamatergic neuron function

Neural Regeneration Research, Journal Year: 2023, Volume and Issue: 18(11), P. 2449 - 2458

Published: March 11, 2023

Sleep benefits the restoration of energy metabolism and thereby supports neuronal plasticity cognitive behaviors. Sirt6 is a NAD+-dependent protein deacetylase that has been recognized as an essential regulator because it modulates various transcriptional regulators metabolic enzymes. The aim this study was to investigate influence on cerebral function after chronic sleep deprivation (CSD). We assigned C57BL/6J mice control or two CSD groups subjected them AAV2/9-CMV-EGFP AAV2/9-CMV-Sirt6-EGFP infection in prelimbic cortex (PrL). then assessed functional connectivity (FC) using resting-state MRI, neuron/astrocyte kinetics analysis; dendritic spine densities sparse-labeling; miniature excitatory postsynaptic currents (mEPSCs) action potential (AP) firing rates whole-cell patch-clamp recordings. In addition, we evaluated cognition via comprehensive set behavioral tests. Compared with controls, significantly decreased (P < 0.05) PrL CSD, accompanied by deficits FC between accumbens nucleus, piriform cortex, motor somatosensory olfactory tubercle, insular cerebellum. overexpression reversed CSD-induced impairment reduced FC. Our analysis [1-13C] glucose [2-13C] acetate showed Glu4 GABA2 synthesis, which could be fully restored forced expression. Furthermore, decreases AP well frequency amplitude mEPSCs pyramidal neurons. These data indicate can improve regulating PrL-associated network, metabolism, glutamatergic neurotransmission. Thus, activation may have novel strategy for treating disorder-related diseases.

Language: Английский

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The regulation of glutamatergic nervous system in sleep-wake states and general anesthesia

Brain Research Bulletin, Journal Year: 2025, Volume and Issue: unknown, P. 111220 - 111220

Published: Jan. 1, 2025

Language: Английский

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Effect of Painful Stimuli on PVNCRH Neurons: Implications for States of Consciousness Under Isoflurane Anesthesia

Anesthesia & Analgesia, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 18, 2025

BACKGROUND: Many patients undergoing surgery experience accompanying pain symptoms preoperatively. The impact of painful stimuli on general anesthesia remains largely unknown. Corticotrophin-releasing hormone neurons in the paraventricular nucleus hypothalamus (PVN CRH neurons) are crucial central stress hubs that respond to stimuli. These also participate regulating processes such as sleep and anesthesia. Natural reward can inhibit PVN relieve stress-induced behavioral changes, but effect natural process with is not clear. In this study, we assessed isoflurane its potential neural mechanism. We investigated therapy for alleviating METHODS: righting reflex test cortical electroencephalography (EEG) were used measures consciousness complete Freund’s adjuvant (CFA)-injected mice during EEG burst-suppression ratios (BSR) assess depth expression c-Fos, fiber photometry recording, brain slice electrophysiology determine neuronal activity changes after CFA injection or 10% sucrose treatment. Finally, chemogenetic technology was specifically manipulate neurons. RESULTS: Compared saline-injected mice, CFA-injected exhibited an increased mean[SD] induction time (354[48] s vs 258[30] s, P = .0001) a reduced BSR (60.1[10.3] % 81.5[9.76] %, .002). c-Fos (3667[706] 1735[407], .0002) enhanced population (33.4[13.6] 1.23[3.57] .0009). Chemogenetic suppression reversed abnormalities mice. accelerated (252[24] 324[36] .003) (84.8[5.36] 57.7[14.3] .0005). activation CONCLUSIONS: Painful affect by activating neurons, which implies these modulate Additionally, alleviates inhibiting

Language: Английский

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The paraventricular nucleus of the hypothalamus: a key node in the control of behavioural states

The Journal of Physiology, Journal Year: 2025, Volume and Issue: unknown

Published: March 22, 2025

Abstract The paraventricular nucleus (PVN) of the hypothalamus contains diverse populations neuropeptide‐producing neurons. These include neurons that synthesise oxytocin, vasopressin, corticotropin‐releasing hormone, thyrotropin‐releasing hormone and somatostatin. While it is well established these control secretion neuroendocrine hormones, there growing evidence they also expression important homeostatic behaviours. Here we review recent data showing a critical role PVN in controlling arousal, social behaviour, defensive behaviour pain. Collectively, this suggests key node wider neural network behavioural states. image

Language: Английский

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Emotion in action: When emotions meet motor circuits

Neuroscience & Biobehavioral Reviews, Journal Year: 2023, Volume and Issue: 155, P. 105475 - 105475

Published: Nov. 22, 2023

The brain is a remarkably complex organ responsible for wide range of functions, including the modulation emotional states and movement. Neuronal circuits are believed to play crucial role in integrating sensory, cognitive, information ultimately guide motor behavior. Over years, numerous studies employing diverse techniques such as electrophysiology, imaging, optogenetics have revealed network neural involved regulation or processes. Emotions can exert substantial influence on performance, encompassing both everyday activities pathological conditions. aim this review explore how shape movements by connecting processing circuits. We first provide comprehensive overview impact different control humans rodents. In line with behavioral studies, we set out identify emotion-related structures capable modulating output, behaviorally anatomically. extensively connected system. These drive behavior, essential survival, but also continuously ongoing summary, investigation intricate relationship between emotion movement offers valuable insights into human opportunities enhance holds promise improving mental physical health. This integrates findings from multiple scientific approaches, anatomical tracing, circuit-based dissection, conducted animal subjects. By incorporating these methodologies, present current understanding physiological

Language: Английский

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The brain in chronic insomnia and anxiety disorder: a combined structural and functional fMRI study

Frontiers in Psychiatry, Journal Year: 2024, Volume and Issue: 15

Published: June 4, 2024

Background Chronic insomnia disorder (CID) is usually associated with Generalized Anxiety Disorder (GAD), which may change brain structure and function. However, the possible markers, imaging characteristics, pathophysiology are unknown. Objective To look at probable pathogenesis of CID in combination GAD. Methods A total 57 patients concomitant GAD healthy controls (HC) were enrolled. Voxel-based morphometry (VBM) functional connectivity (FC) utilized to measure gray matter volume (GMV) changes. Correlation analysis was identify relationships between changes clinical characteristics. Results Patients had decreased GMV left cerebellum, right cerebellar peduncle, insula; increased FC cerebellum angular gyrus, as well insula anterior cingulate gyrus; several areas, including middle gyrus superior postcentral gyrus. These related data could be used relevant features, better understand etiology. Conclusion The intensity strongly severity anxiety. lower interpreted an characteristic CID. Reduced insula, aberrant function prefrontal lobe, contribute Abnormal patients’ complaints.

Language: Английский

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Distinct glutamatergic projections of the posteroventral medial amygdala play different roles in arousal and anxiety

JCI Insight, Journal Year: 2024, Volume and Issue: 9(14)

Published: June 6, 2024

Sleep disturbance usually accompanies anxiety disorders and exacerbates their incidence rates. The precise circuit mechanisms remain poorly understood. Here, we found that glutamatergic neurons in the posteroventral medial amygdala (MePVGlu neurons) are involved arousal anxiety-like behaviors. Excitation of MePVGlu not only promoted wakefulness but also increased Different projections played various roles regulating behaviors sleep-wakefulness. through MePVGlu/posteromedial cortical amygdaloid area (PMCo) pathway MePVGlu/bed nucleus stria terminals (BNST) pathway. In contrast, MePVGlu/ventromedial hypothalamus (VMH) Chronic sleep levels reduced reparative sleep, accompanied by enhanced excitability MePVGlu/PMCo MePVGlu/VMH circuits suppressed responses BNST. Inhibition could rescue chronic deprivation-induced phenotypes. Our findings provide important for disturbance-induced hyperarousal response obsessive behavior expected to a promising strategy treating sleep-related psychiatric insomnia.

Language: Английский

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CaMKIIa Neurons of the Ventromedial Hypothalamus Mediate Wakefulness and Anxiety-like Behavior

Neurochemical Research, Journal Year: 2023, Volume and Issue: 48(8), P. 2463 - 2475

Published: April 4, 2023

Language: Английский

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Acquiring Social Safety Engages Oxytocin Neurons in the Supraoptic Nucleus: Role of Magel2 Deficiency

Neuroendocrinology, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 16

Published: April 4, 2024

<b><i>Introduction:</i></b> Exposure to social trauma may alter engagement with both fear-related and unrelated stimuli long after. Intriguingly, how simultaneous discrimination of fear safety is affected in neurodevelopmental conditions remains underexplored. The role the neuropeptide oxytocin established behaviors yet unexplored during such a challenge post-social trauma. <b><i>Methods:</i></b> Using <i>Magel2</i> knockout mice, an animal model Prader-Willi syndrome (PWS) Schaaf-Yang (SYS), we tested memory after modified conditioning task. Additionally, tracked activity neurons supraoptic (SON) paraventricular (PVN) nuclei hypothalamus by fiber photometry, as animals were simultaneously presented choice between safe cue recall. <b><i>Results:</i></b> Male KO mice trained females electrical footshocks avoided unfamiliar males recalls, lasting even week post-conditioning. On contrary, WT only days rather than Inability overcome avoidance associated reduced SON but not PVN. <b><i>Conclusion:</i></b> In preclinical PWS/SYS, demonstrated region-specific deficit neuron behavioral generalization safety. Insights from this study add our understanding action brain at intersection PWS/SYS.

Language: Английский

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