Neuron-derived Extracellular Vesicles in Blood Reveal Effects of Exercise in Alzheimer’s Disease DOI Creative Commons
Francheska Delgado‐Peraza, Carlos Nogueras‐Ortiz, Anja Hviid Simonsen

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: April 5, 2023

Abstract Background Neuron-derived extracellular vesicles (NDEVs) in blood may be used to derive biomarkers for effects of exercise Alzheimer’s disease (AD). For this purpose, we studied changes neuroprotective proteins proBDNF, BDNF and humanin plasma NDEVs from patients with mild moderate AD participating the randomized controlled trial (RCT) ADEX. Methods were quantified immunocaptured 95 ADEX participants, into control groups, collected at baseline 16-weeks. Exploratorily, also NDEV levels putative exerkines known respond peripheral tissues. Results increased group, especially APOE ε4 carriers, but remained unchanged group. Inter-correlations between observed maintained after exercise. unchanged. Conclusions Findings suggest that cognitive benefits could mediated by upregulation factors NDEVs. Additionally, our results indicate subjects carrying are more responsive physical activity. Unchanged activity imply engages different pathways neurons Future studies should aim expand upon duration, intensity, type early additional neurodegenerative disorders. Trial registration: The Effect Physical Exercise Alzheimer Patients (ADEX) was registered as ClinicalTrials.gov Identifier: NCT01681602 first submitted on April 30, 2012 met QC criteria September 5, 2012.

Language: Английский

Neuron-derived extracellular vesicles in blood reveal effects of exercise in Alzheimer’s disease DOI Creative Commons
Francheska Delgado‐Peraza, Carlos Nogueras‐Ortiz, Anja Hviid Simonsen

et al.

Alzheimer s Research & Therapy, Journal Year: 2023, Volume and Issue: 15(1)

Published: Sept. 20, 2023

Abstract Background Neuron-derived extracellular vesicles (NDEVs) in blood may be used to derive biomarkers for the effects of exercise Alzheimer’s disease (AD). For this purpose, we studied changes neuroprotective proteins proBDNF, BDNF, and humanin plasma NDEVs from patients with mild moderate AD participating randomized controlled trial (RCT) ADEX. Methods were quantified immunocaptured 95 ADEX participants, into control groups, collected at baseline 16 weeks. Exploratorily, also NDEV levels putative exerkines known respond peripheral tissues. Results increased group, especially APOE ε4 carriers, but remained unchanged group. Inter-correlations between observed maintained after exercise. unchanged. Conclusions Findings suggest that cognitive benefits could mediated by upregulation factors NDEVs. Additionally, our results indicate subjects carrying are more responsive physical activity. Unchanged activity imply engages different pathways neurons Future studies should aim expand upon duration, intensity, type early additional neurodegenerative disorders. Trial registration The Effect Physical Exercise Alzheimer Patients (ADEX) was registered ClinicalTrials.gov on April 30, 2012 identifier NCT01681602. Graphical abstract

Language: Английский

Citations

27
Single‐extracellular vesicle (EV) analyses validate the use of L1 Cell Adhesion Molecule (L1CAM) as a reliable biomarker of neuron‐derived EVs DOI Creative Commons
Carlos Nogueras‐Ortiz, Erden Eren, Pamela J. Yao

et al.

Journal of Extracellular Vesicles, Journal Year: 2024, Volume and Issue: 13(6)

Published: June 1, 2024

Abstract Isolation of neuron‐derived extracellular vesicles (NDEVs) with L1 Cell Adhesion Molecule (L1CAM)‐specific antibodies has been widely used to identify blood biomarkers CNS disorders. However, full methodological validation requires demonstration L1CAM in individual NDEVs and lower levels or absence EVs from other cells. Here, we multiple single‐EV techniques establish the neuronal origin determine abundance L1CAM‐positive human blood. epitopes ectodomain are shown be co‐expressed on single‐EVs proteins β‐III‐tubulin, GAP43, VAMP2, which increase parallel enrichment EVs. Levels carrying VAMP2 β‐III‐tubulin range 30% 63%, contrast 0.8%–3.9% L1CAM‐negative Plasma fluid‐phase does not bind single‐EVs. Our findings support use as a target for isolating plasma leveraging their cargo reflecting function.

Language: Английский

Citations

13
Exploring genetic associations and drug targets for mitochondrial proteins and schizophrenia risk DOI Creative Commons
Wenxi Sun, Ping Sun, Jin Li

et al.

Schizophrenia, Journal Year: 2025, Volume and Issue: 11(1)

Published: Jan. 25, 2025

Numerous observational studies have highlighted associations between mitochondrial dysfunction and schizophrenia (SCZ), yet the causal relationship remains elusive. This study aims to elucidate link mitochondria-associated proteins SCZ. We used summary data from a genome-wide association (GWAS) of 66 in 3,301 individuals Europe, as well GWAS on large, multi-ethnic ancestry SCZ, involving 76,755 cases 243,649 controls. conducted bidirectional two-sample Mendelian randomization (MR) analyses, with inverse variance weighting (IVW) primary method. To account for multi-directionality ensure robustness, we included MR-Egger, weighted median (WM), mode, simple mode methods supplementary sensitivity analyses. Moreover, explored catalog Drug-Gene Interaction Database (DGIdb) identify evaluate potential therapeutic targets. MR analysis revealed significant genetically determined ETHE1 (OR: 1.06), SOD 0.97), CALU3 1.03), C1QBP 1.05) According reverse analysis, was shown SCZ CA5A 1.09), DLD 1. 08), AIF1 0.93), SerRS 0.93) MULA NFKB1 0.77). After conducting gene-drug HRG, F12, GPLD1, C1R, BCHE, CFH, PON1, were identified promising present reveals offering valuable insights into disease's pathogenicity identifying targets drug development.

Language: Английский

Citations

0
Potential of extracellular vesicle cargo as molecular signals in Schizophrenia: a scoping review DOI Creative Commons

G Shivaprakash,

Smita Shenoy, Dinesh Upadhya

et al.

Schizophrenia, Journal Year: 2025, Volume and Issue: 11(1)

Published: Feb. 12, 2025

Abstract The diagnosis of schizophrenia (SCZ) primarily relies on clinical history and mental status assessments by trained professionals. There has been a search for biomarkers to facilitate laboratory diagnosis. Since extracellular vesicles (EVs) communicate with brain cells can easily cross blood-brain barrier, there is increased interest among experts explore them as potential molecular signals disease detection. A scoping review was conducted provide comprehensive summary the existing literature identify differentially expressed in EVs isolated from SCZ patients. methodological framework outline provided Arksey O’Malley employed conduct this review. systematic using string across four databases, ultimately leading selection 24 relevant studies. Over 1122 biomolecules were identified extracted biological fluids tissues that be categorized RNAs, proteins, metabolites. Among them, 83 validated signals, which included metabolites, circRNAs, lncRNAs, miRNAs, proteins. These found affect cellular receptors intracellular pathways, neurotransmitters, mitochondrial functions, immune-related metabolic could serve

Language: Английский

Citations

0
Neuron-Derived Extracellular Vesicles: Emerging Regulators in Central Nervous System Disease Progression DOI
Sitong Liu,

A. S. Feng,

Zhigang Li

et al.

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: May 6, 2025

Language: Английский

Citations

0
Examination of the enrichment of neuronal extracellular vesicles from cell conditioned media and human plasma using an anti-NCAM immunocapture bead approach DOI Creative Commons
Mary E.W. Collier, Natalie Allcock, Nicolas Sylvius

et al.

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

Published: May 14, 2025

Abstract Background The isolation of neuron-derived extracellular vesicles (nEVs) from biofluids offers the potential to discover novel biomarkers aid in diagnosis and treatment psychiatric neurodegenerative diseases. A few studies have used anti-NCAM antibody-bead-based immunocapture enrich nEVs plasma, some with little method validation. We therefore examined detail this for nEV enrichment. Methods EVs were isolated SH-SY5Y cell-conditioned media by precipitation, or plasma using size exclusion chromatography. characterised nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM) immunoblot analysis. SH-SY5Y-EVs incubated beads flow cytometry, scanning (SEM). Immunocaptured plasma-derived a sensitive NCAM ELISA, SEM qPCR miRNAs. Results Characterisation SH-SY5Y-derived revealed expected distributions NTA, presence EV markers analysis, cup-shaped morphology TEM. Anti-NCAM beads, but not anti-L1CAM IgG captured NCAM-positive as shown cytometry Both visualised on surface SEM. ELISA detected antigen immunocaptured beads. many miRNAs total plasma-EVs high expression hsa-miR-16-5p, hsa-miR-451a hsa-miR-126-3p. However, only between two seven anti-NCAM-beads three blood donors. Finally, tissue distribution that these are enriched tissues organs such vessels, lung, bone, thyroid heart, brain-derived Discussion: This study indicates can efficiently cell culture conditioned media. levels small volumes possibly too low enable efficient subsequent miRNA Other neuron-specific required processing patient samples where likely be low, allow clinical cargo

Language: Английский

Citations

0
Reduced numbers of naïve CD4 + T cells and an altered CD4/CD8 balance in depressed common variable immune deficiency (CVID) patients. Is thymosin-α1 a possible treatment? DOI Creative Commons
Olivia R. Manusama,

Sajni Singh,

Rik A. Brooimans

et al.

International Immunopharmacology, Journal Year: 2023, Volume and Issue: 119, P. 110168 - 110168

Published: April 20, 2023

In the 1990's macrophage-T-cell-theory of depression was posed stating that low grade inflammation and an abnormal T cell system destabilize development function emotional brain in such a way, individuals become ultrasensitive to stress. Recently we gathered evidence indeed higher frequencies CD4+ memory cells, lower naive CD4 + CD8 cells (the latter two part elicited by Cytomegalovirus, CMV, infection) are characteristic Major Depressive Disorder (MDD). MDD patients with history childhood trauma severe monocytes inflammatory activated. Low defects have also been reported Common Variable Immune Deficiency (CVID) (next antibody production defects). CVID show prevalence mild depression. The aim this study determine monocyte activation without This confirms CMV independent decreases frequency naïve it de novo shows dependent increase expression genes monocytes. additionally characterized while lacking activation. conclusion, depressed abnormalities comparable regular MDD. These presently targeted thymosin α1 open-label proof concept trial.

Language: Английский

Citations

5
Urinary Astrocyte-derived Extracellular Vesicles: A Non-invasive Tool for Capturing HumanIn VivoMolecular "Movies" of Brain DOI Open Access
Xin‐hui Xie, Mianmian Chen,

Shu‐xian Xu

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 13, 2024

Abstract The identification of particularly individual-level biomarkers, for certain central nervous system (CNS) diseases remains challenging. A recent approach involving the enrichment brain-derived extracellular vesicles (BDEVs) from peripheral blood has emerged as a promising method to obtain direct in vivo CNS data, bypassing blood-brain barrier. However, rapidly evolving ( e.g. , weeks or even days), Nyquist-Shannon sampling theorem dictates need high-frequency rate. Obviously, daily collection cerebrospinal fluid human subjects is impractical. Thus, we innovated novel isolate astrocyte-derived EVs urine (uADEVs). It involves three main steps: 1) concentrating samples, 2) isolating total (uTEVs) using ultracentrifugation, and 3) an anti-glutamate/aspartate transporter (GLAST) antibody GLAST + uTEVs. Subsequently, confirmed identity these uADEVs transmission electron microscopy, nanoparticle tracking analysis, western blotting, measurement astrocyte-related neurotrophins. Furthermore, applied protocol depict detailed trajectory N-methyl-d-aspartic acid receptor (NMDAR) subunit zeta-1 (GluN1) anti-NMDAR encephalitis patient, demonstrated potential this capturing intricate trajectories CNS-specific molecular signals at individual level. This non-invasive enables frequent sampling, up half-daily, analogous “movies” brain, coupled with appropriate signal processing algorithms, holds promise identifying biomarkers illuminating etiology by precise target molecules.

Language: Английский

Citations

1
Brain metabolic profiling of schizophrenia: a path towards a better understanding of the neuropathogenesis of psychosis DOI
Martina Rossetti, Stefano Stanca, Leona Bokulic Panichi

et al.

Metabolic Brain Disease, Journal Year: 2024, Volume and Issue: 40(1)

Published: Nov. 21, 2024

Language: Английский

Citations

1
The role of Extracellular Genomic Materials (EGMs) in psychiatric disorders DOI Creative Commons
Ayse Kurtulmuş, Cemal Çağıl Koçana, Selin Fulya Toprak

et al.

Translational Psychiatry, Journal Year: 2023, Volume and Issue: 13(1)

Published: July 18, 2023

Abstract Extracellular Genomic Materials (EGMs) are the nucleic acids secreted or released from all types of cells by endogenous exogenous stimuli through varying mechanisms into extracellular region and inevitably to biological fluids. EGMs could be found as free, protein-bound, and/ with vesicles. can potentially have immunophenotypic and/or genotypic characteristics a cell origin, travel distant organs, interact new microenvironment. To achieve all, might bi-directionally transit membranes, including blood–brain barrier. Such ability provides transfer any information related pathophysiological changes in psychiatric disorders brain other organ systems vice versa. In this article, many aspects been elegantly reviewed, their potential diagnosis biomarkers, application treatment modalities, functional effects pathophysiology disorders. The were studied under subgroups Schizophrenia spectrum disorders, bipolar disorder, depressive an autism provide robust promising tool clinics for prognosis diagnosis. successful modalities further encouraging outcomes researchers clinicians

Language: Английский

Citations

3