Astrocytes regulate vascular endothelial responses to simulated deep space radiation in a human organ-on-a-chip model

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

Published: Aug. 30, 2022

Central nervous system (CNS) damage by galactic cosmic ray radiation is a major health risk for human deep space exploration. Simulated rays or their components, especially high Z-high energy particles such as 56Fe ions, cause neurodegeneration and neuroinflammation in rodent models. CNS can be partially mediated the blood-brain barrier, which regulates systemic interactions between rest of body. Astrocytes are cellular regulators barrier permeability that also modulate neuronal health. However, astrocyte roles regulating responses to remain little understood, tissue analogs. In this work, we used novel high-throughput organ-on-a-chip evaluate impairments functions 1-7 days after exposure 600 MeV/n simplified simulated rays. We show causes vascular permeability, oxidative stress, inflammation delayed activation pattern resembling brain injury. Furthermore, our results indicate astrocytes have dual role responses: they exacerbate acutely irradiation, followed switching more protective phenotype reducing stress pro-inflammatory cytokine chemokine secretion during subacute stage.

Language: Английский

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Effect of hyperbaric oxygen therapy for non-motor symptoms among patients with Parkinson's disease: A systematic review and meta-analysis

Clinical Rehabilitation, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 7, 2025

Objective To systematically evaluate the efficacy of hyperbaric oxygen therapy for non-motor symptoms in patients with Parkinson's disease. Data sources A systematic search was performed across several databases, including Chinese Science and Technology Periodical Database, Web Science, SinoMed, PubMed, Cochrane Library, Embase Wanfang databases up to 1 December 2024. Studies considered inclusion comprised randomised controlled trials pre–post control studies. Review methods The authors conducted data extraction literature screening procedures independently. selected studies’ quality evaluated using risk bias technique. Manager 5.3 used conduct meta-analyses, while Stata 15.0 utilised sensitivity analysis assess publication bias. Results Sixteen studies a total 1324 individuals satisfied criteria. results meta-analysis showed that significantly improved scores on Hamilton Anxiety Scale Depression compared baseline (both p < 0.05). Additionally, improvements were observed Montreal Cognitive Assessment, Mini-Mental State Examination, Disease Sleep Scale, Pittsburgh Quality Index, Kubota's Drinking Water Test Unified Rating III. Improvements sleep efficiency extension time also noted controls (all Conclusion findings indicate effectively alleviates such as anxiety, depression, cognitive impairments, disturbances, swallowing dysfunction, well improving motor function disease patients. Since protocol had significant differences between studies, further prospective rigorous methodology are needed.

Language: Английский

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The Retinal Age Gap as a Marker of Accelerated Aging in the Early Course of Schizophrenia

Schizophrenia Bulletin, Journal Year: 2025, Volume and Issue: unknown

Published: April 14, 2025

Abstract Background and Hypothesis Given the available findings confirming accelerated brain aging in schizophrenia (SZ), we conducted a study aimed at verifying whether quantitative retinal morphological data enable age prediction patients present with positive gap (RAG). Study Design Two samples of controls were enrolled: one included 59 SZ 60 controls, all whom underwent optical coherence tomography (OCT) enabling measurement 72 variables. A second sample 65 70 was then combined first sample, to generate database where each subject represented by 28 Four different machine learning (ML) algorithms used for based on z-standardized OCT data. The associations between RAG, demographic, clinical also analyzed. Results Patients from both had significantly higher RAG ranging 5.88 7.44 years depending specific sample. Predictions larger group but fewer variables exhibited relative error. All ML generated similar outcomes regarding age. correlated dose antipsychotic medication severity symptoms. Correlations chronological showed that highest younger patients, about 45 years, it decreased. Conclusions ML-based results corroborated its pharmacological treatment syndrome severity. finding is novel requires replication.

Language: Английский

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Molecular and Cellular Interactions in Pathogenesis of Sporadic Parkinson Disease

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(21), P. 13043 - 13043

Published: Oct. 27, 2022

An increasing number of the population all around world suffer from age-associated neurodegenerative diseases including Parkinson's disease (PD). This disorder presents different signs genetic, epigenetic and environmental origin, molecular, cellular intracellular dysfunction. At molecular level, α-synuclein (αSyn) was identified as principal molecule constituting Lewy bodies (LB). The gut microbiota participates in pathogenesis PD may contribute to loss dopaminergic neurons through mitochondrial most important pathogenetic link is an imbalance Ca2+ ions, which associated with redox cells increased generation reactive oxygen species (ROS). In this review, factors that cause these disorders their cause-and-effect relationships are considered. As a constituent factors, example organophosphates (OPs) also reviewed. role endothelial damage discussed, 'triple hit hypothesis' proposed modification Braak's dual one. absence effective therapies for diseases, more evidence emerging about positive impact nutritional structure healthy lifestyle on state blood vessels risk developing diseases.

Language: Английский

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A Vascular-Centric Approach to Autism Spectrum Disorders

Neuroscience Insights, Journal Year: 2024, Volume and Issue: 19

Published: Jan. 1, 2024

Brain development and function are highly reliant on adequate establishment maintenance of vascular networks. Early impairments in health can impact brain maturation energy metabolism, which may lead to neurodevelopmental anomalies. Our recent work not only provides novel insights into the cerebrovascular networks but also emphasizes importance their well-being for proper maturation. In particular, we have demonstrated that endothelial dysfunction autism spectrum disorders (ASD) mouse models is causally related altered behavior metabolism. prenatal human brain, cells change metabolic states second trimester. Such findings highlight need identify new cellular molecular players disorders, raising awareness about a healthy vasculature development. It thus essential shift mostly neuronal point view research ASD other include features.

Language: Английский

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Interactions of Polychlorinated Biphenyls and Their Metabolites with the Brain and Liver Transcriptome of Female Mice

ACS Chemical Neuroscience, Journal Year: 2024, Volume and Issue: 15(21), P. 3991 - 4009

Published: Oct. 11, 2024

Exposure to polychlorinated biphenyls (PCBs) is linked neurotoxic effects. This study aims close knowledge gaps regarding the specific modes of action PCBs in female C57BL/6J mice (>6 weeks) orally exposed for 7 weeks a human-relevant PCB mixture (MARBLES mix) at 0, 0.1, 1, and 6 mg/kg body weight/day. hydroxylated (OH-PCBs) levels were quantified brain, liver, serum; RNA sequencing was performed striatum, prefrontal cortex, metabolomic analyses striatum. Profiles but not their metabolites similar all tissues. In exposure activated oxidative phosphorylation respiration pathways, while suppressing axon guidance pathway. significantly changed expression genes associated with neurodevelopmental neurodegenerative diseases impacting pathways like growth hormone synthesis dendrite development. did affect striatal metabolome. contrast which showed activation metabolic processes following induction cytochrome P450 enzymes, xenobiotic processing altered by either brain region. Network analysis revealed complex interactions between individual (e.g., PCB28 [2,4,4′-trichlorobiphenyl]) differentially expressed (DEGs), underscoring need characterize association DEGs. These findings enhance understanding mechanisms potential implications human health.

Language: Английский

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Hypoxia-inducible factor 1 protects neurons from Sarm1-mediated neurodegeneration

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

Published: Jan. 18, 2025

Abstract The Sarm1 NAD + hydrolase drives neurodegeneration in many contexts, but how activity is regulated remains poorly defined. Using CRISPR/Cas9 screening, we found loss of VHL suppressed Sarm1-mediated cellular degeneration. normally promotes O 2 -dependent constitutive ubiquitination and degradation hypoxia-inducible factor 1 (HIF-1), during hypoxia, HIF-1 stabilized regulates gene expression. We observed neuroprotection after depletion or other factors required for degradation, expression a non-ubiquitinated variant led to even stronger blockade axon degeneration mammals Drosophila . Neuroprotection DNA binding, prolonged expression, resulted broad changes. Unexpectedly, prevented the precipitous driven by activation neurons, despite being intrinsic TIR domain. Our work argues hypoxia inhibits through transcriptional changes, rendering neurons less sensitive when hypoxic state. Competing interests Marc Freeman co-founder Nura Bio, biotech startup pursuing novel neuroprotective therapies including SARM1 inhibition. remaining authors declare no competing interests.

Language: Английский

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OCT and OCT Angiography Offer New Insights and Opportunities in Schizophrenia Research and Treatment

Frontiers in Digital Health, Journal Year: 2022, Volume and Issue: 4

Published: Feb. 18, 2022

The human retina and retinal imaging technologies continue to increasingly gain the attention of schizophrenia researchers. With same embryologic origin as brain, offers a window into neurovascular changes that may underlie disease. Recently, two have already revolutionized field ophthalmology, optical coherence tomography (OCT), functional extension this, angiography (OCTA), gained traction. Together, these non-invasive allow for microscopic both structural vascular features retina. ease use no side effects, devices are likely prove powerful digital health tools in study treatment schizophrenia. They also key discovering disease relevant biomarkers underly neurodevelopmental neurodegenerative aspects conditions such

Language: Английский

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Altered delay discounting in neurodegeneration: insight into the underlying mechanisms and perspectives for clinical applications

Neuroscience & Biobehavioral Reviews, Journal Year: 2023, Volume and Issue: 146, P. 105048 - 105048

Published: Jan. 18, 2023

Steeper delay discounting (i.e., the extent to which future rewards are perceived as less valuable than immediate ones) has been proposed a transdiagnostic process across different health conditions, in particular psychiatric disorders. Impulsive decision-making is hallmark of neurodegenerative conditions but little known about domain conditions. We reviewed studies on patients with Parkinson's disease (PD) and dementia (Alzheimer's / AD or frontotemporal FTD). that could be an early marker process. developed idea altered associated overlapping distinct neurocognitive mechanisms diseases: dopaminergic-related disorders reward processing PD, memory/projection deficits due medial temporal atrophy AD, modified orbitofrontal FTD. Neurodegeneration provide framework decipher neuropsychological value-based decision-making. Further, become interest clinical practice, for differential diagnosis.

Language: Английский

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Neurovascular crosstalk and cerebrovascular alterations: an underestimated therapeutic target in autism spectrum disorders

Frontiers in Cellular Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: Aug. 24, 2023

Normal brain development, function, and aging critically depend on unique characteristics of the cerebrovascular system. Growing evidence indicated that defects can have irreversible effects brain, these been implicated in various neurological disorders, including autism spectrum disorder (ASD). ASD is a neurodevelopmental with heterogeneous clinical manifestations anatomical changes. While extensive research has focused neural abnormalities underlying ASD, role vasculature this remains poorly understood. Indeed, significance contributions to consistently underestimated. In work, we discuss neurovascular crosstalk during embryonic development highlight recent findings alterations individuals ASD. We also potential vascular-based therapy for Collectively, investigations demonstrate be considered disease.

Language: Английский

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