26 results on '"Vandendriessche C"'
Search Results
2. The choroid plexus epithelium as a novel player in the stomach-brain axis during Helicobacter infection
- Author
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Gorlé, N., Blaecher, C., Bauwens, E., Vandendriessche, C., Balusu, S., Vandewalle, J., Van Cauwenberghe, C., Van Wonterghem, E., Van Imschoot, G., Liu, C., Ducatelle, R., Libert, C., Haesebrouck, F., Smet, A., and Vandenbroucke, R.E.
- Published
- 2018
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3. P014 Behaviour in mice with chronic DSS colitis mimics fatigue in IBD and is associated with neuroinflammation
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Truyens, M, primary, Lernout, H, additional, Vandendriessche, C, additional, Bruggeman, A, additional, Xie, J, additional, De Vos, M, additional, Vermeirssen, V, additional, Vandenbroucke, R, additional, and Laukens, D, additional
- Published
- 2023
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4. P005 Persistent transcriptional reprogramming in the choroid plexus during chronic colitis: towards understanding persistent fatigue in patients with quiescent inflammatory bowel disease?
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Bruggeman, A, primary, Vandendriessche, C, additional, De Vos, M, additional, Vandenbroucke, R, additional, and Laukens, D, additional
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- 2019
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5. Fonctions exécutives en cas de psychose schizophrénique
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De Hert, Marc, Lecompte, D, Janssen, F, De Bleeker, E, Vandendriessche, C, Hulselmans, J, Peuskens, Jozef, Hellebuyck, H, and Wampers, Martien
- Abstract
ispartof: Neurone vol:21 issue:1 pages:1-8 status: published
- Published
- 2007
6. The effect of movement speed on upper-limb coupling strength
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Swinnen, S. P., Walter, C. B., Serrien, D. J., and Vandendriessche, C.
- Published
- 1992
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7. Microfluidic Interfaces for Chronic Bidirectional Access to the Brain.
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Marcigaglia S, De Plus R, Vandendriessche C, Schiltz E, Cuypers ML, Cools J, Hoffman LD, Vandenbroucke RE, Dewilde M, and Haesler S
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- Animals, Mice, Blood-Brain Barrier metabolism, Microfluidics methods, Brain metabolism
- Abstract
Two-photon polymerization (TPP) is an additive manufacturing technique with micron-scale resolution that is rapidly gaining ground for a range of biomedical applications. TPP is particularly attractive for the creation of microscopic three-dimensional structures in biocompatible and noncytotoxic resins. Here, TPP is used to develop microfluidic interfaces which provide chronic fluidic access to the brain of preclinical research models. These microcatheters can be used for either convection-enhanced delivery (CED) or for the repeated collection of liquid biopsies. In a brain phantom, infusions with the micronozzle result in more localized distribution clouds and lower backflow compared to a control catheter. In mice, the delivery interface enables faster, more precise, and physiologically less disruptive fluid injections. A second microcatheter design enables repeated, longitudinal sampling of cerebrospinal fluid (CSF) over time periods as long as 250 days. Moreover, further in vivo studies demonstrate that the blood-CSF barrier is intact after chronic implantation of the sampling interface and that samples are suitable for downstream molecular analysis for the identification of nucleic acid- or peptide-based biomarkers. Ultimately, the versatility of this fabrication technique implies a great translational potential for simultaneous drug delivery and biomarker tracking in a range of human neurological diseases., (© 2024 The Author(s). Advanced Healthcare Materials published by Wiley‐VCH GmbH.)
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- 2024
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8. Involvement of the choroid plexus in Alzheimer's disease pathophysiology: findings from mouse and human proteomic studies.
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Delvenne A, Vandendriessche C, Gobom J, Burgelman M, Dujardin P, De Nolf C, Tijms BM, Teunissen CE, Schindler SE, Verhey F, Ramakers I, Martinez-Lage P, Tainta M, Vandenberghe R, Schaeverbeke J, Engelborghs S, De Roeck E, Popp J, Peyratout G, Tsolaki M, Freund-Levi Y, Lovestone S, Streffer J, Bertram L, Blennow K, Zetterberg H, Visser PJ, Vandenbroucke RE, and Vos SJB
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- Animals, Humans, Mice, Amyloid beta-Protein Precursor metabolism, Amyloid beta-Protein Precursor genetics, Proteome metabolism, Male, Female, Mice, Inbred C57BL, Choroid Plexus metabolism, Alzheimer Disease metabolism, Alzheimer Disease cerebrospinal fluid, Proteomics, Mice, Transgenic, Disease Models, Animal
- Abstract
Background: Structural and functional changes of the choroid plexus (ChP) have been reported in Alzheimer's disease (AD). Nonetheless, the role of the ChP in the pathogenesis of AD remains largely unknown. We aim to unravel the relation between ChP functioning and core AD pathogenesis using a unique proteomic approach in mice and humans., Methods: We used an APP knock-in mouse model, APP
NL-G-F , exhibiting amyloid pathology, to study the association between AD brain pathology and protein changes in mouse ChP tissue and CSF using liquid chromatography mass spectrometry. Mouse proteomes were investigated at the age of 7 weeks (n = 5) and 40 weeks (n = 5). Results were compared with previously published human AD CSF proteomic data (n = 496) to identify key proteins and pathways associated with ChP changes in AD., Results: ChP tissue proteome was dysregulated in APPNL-G-F mice relative to wild-type mice at both 7 and 40 weeks. At both ages, ChP tissue proteomic changes were associated with epithelial cells, mitochondria, protein modification, extracellular matrix and lipids. Nonetheless, some ChP tissue proteomic changes were different across the disease trajectory; pathways related to lysosomal function, endocytosis, protein formation, actin and complement were uniquely dysregulated at 7 weeks, while pathways associated with nervous system, immune system, protein degradation and vascular system were uniquely dysregulated at 40 weeks. CSF proteomics in both mice and humans showed similar ChP-related dysregulated pathways., Conclusions: Together, our findings support the hypothesis of ChP dysfunction in AD. These ChP changes were related to amyloid pathology. Therefore, the ChP could become a novel promising therapeutic target for AD., (© 2024. The Author(s).)- Published
- 2024
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9. Safety and efficacy of faecal microbiota transplantation in patients with mild to moderate Parkinson's disease (GUT-PARFECT): a double-blind, placebo-controlled, randomised, phase 2 trial.
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Bruggeman A, Vandendriessche C, Hamerlinck H, De Looze D, Tate DJ, Vuylsteke M, De Commer L, Devolder L, Raes J, Verhasselt B, Laukens D, Vandenbroucke RE, and Santens P
- Abstract
Background: Dysregulation of the gut microbiome has been implicated in Parkinson's disease (PD). This study aimed to evaluate the clinical effects and safety of a single faecal microbiota transplantation (FMT) in patients with early-stage PD., Methods: The GUT-PARFECT trial, a single-centre randomised, double-blind, placebo-controlled trial was conducted at Ghent University Hospital between December 01, 2020 and December 12, 2022. Participants (aged 50-65 years, Hoehn and Yahr stage 2) were randomly assigned to receive nasojejunal FMT with either healthy donor stool or their own stool. Computer-generated randomisation was done in a 1:1 ratio through permutated-block scheduling. Treatment allocation was concealed for participants and investigators. The primary outcome measure at 12 months was the change in the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor score obtained during off-medication evaluations. Intention-to-treat analysis was performed using a mixed model for repeated measures analysis. This completed trial is registered on ClinicalTrials.gov (NCT03808389)., Findings: Between December 2020 and December 2021, FMT procedures were conducted on 46 patients with PD: 22 in the healthy donor group and 24 in the placebo group. Clinical evaluations were performed at baseline, 3, 6, and 12 months post-FMT. Full data analysis was possible for 21 participants in the healthy donor group and 22 in the placebo group. After 12 months, the MDS-UPDRS motor score significantly improved by a mean of 5.8 points (95% CI -11.4 to -0.2) in the healthy donor group and by 2.7 points (-8.3 to 2.9) in the placebo group (p = 0.0235). Adverse events were limited to temporary abdominal discomfort., Interpretation: Our findings suggested a single FMT induced mild, but long-lasting beneficial effects on motor symptoms in patients with early-stage PD. These findings highlight the potential of modulating the gut microbiome as a therapeutic approach and warrant a further exploration of FMT in larger cohorts of patients with PD in various disease stages., Funding: Flemish PD patient organizations (VPL and Parkili), Research Foundation Flanders (FWO), Biocodex Microbiota Foundation., Competing Interests: JR has received grants from Beneo, Cargill, Colruyt group, Danone, DSM, J&J, MRM/Prodigest, Nestle, Pfizer, and Takeda; and has received consulting and/or speaking fees from Aphea, Biofortis, DSM, Ferring, GSK, Janssen Pharmaceuticals, Metagenics, MSD, MRM/Prodigest, Nutricia, Sanofi, Takeda, Tsumura. RV has received grants from MRM Health, Prodigest, CellCarta, Evox Therapeutics and Sanofi. All other authors declare no competing interests., (© 2024 The Author(s).)
- Published
- 2024
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10. The Spreading and Effects of Human Recombinant α-Synuclein Preformed Fibrils in the Cerebrospinal Fluid of Mice.
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Vandendriessche C, Bruggeman A, Foroozandeh J, Van Hoecke L, Dujardin P, Xie J, Van Imschoot G, Van Wonterghem E, Castelein J, Lucci C, De Groef L, and Vandenbroucke RE
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- Mice, Humans, Animals, Brain metabolism, Dopaminergic Neurons metabolism, Blood-Brain Barrier metabolism, alpha-Synuclein metabolism, Parkinson Disease pathology
- Abstract
Parkinson's disease (PD) patients harbor seeding-competent α-synuclein (α-syn) in their cerebrospinal fluid (CSF), which is mainly produced by the choroid plexus (ChP). Nonetheless, little is known about the role of the CSF and the ChP in PD pathogenesis. To address this question, we used an intracerebroventricular (icv) injection mouse model to assess CSF α-syn spreading and its short- and long-term consequences on the brain. Hereby, we made use of seeding-competent, recombinant α-syn preformed fibrils (PFF) that are known to induce aggregation and subsequent spreading of endogenous α-syn in stereotactic tissue injection models. Here, we show that icv-injected PFF, but not monomers (Mono), are rapidly removed from the CSF by interaction with the ChP. Additionally, shortly after icv injection both Mono and PFF were detected in the olfactory bulb and striatum. This spreading was associated with increased inflammation and complement activation in these tissues as well as leakage of the blood-CSF barrier. Despite these effects, a single icv injection of PFF didn't induce a decline in motor function. In contrast, daily icv injections over the course of 5 days resulted in deteriorated grip strength and formation of phosphorylated α-syn inclusions in the brain 2 months later, whereas dopaminergic neuron levels were not affected. These results point toward an important clearance function of the CSF and the ChP, which could mediate removal of PFF from the brain, whereby chronic exposure to PFF in the CSF may negatively impact blood-CSF barrier functionality and PD pathology., Competing Interests: The authors declare no competing financial interest., (Copyright © 2024 Vandendriessche et al.)
- Published
- 2024
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11. Inflammasome signaling is dispensable for ß-amyloid-induced neuropathology in preclinical models of Alzheimer's disease.
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Srinivasan S, Kancheva D, De Ren S, Saito T, Jans M, Boone F, Vandendriessche C, Paesmans I, Maurin H, Vandenbroucke RE, Hoste E, Voet S, Scheyltjens I, Pavie B, Lippens S, Schwabenland M, Prinz M, Saido T, Bottelbergs A, Movahedi K, Lamkanfi M, and van Loo G
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- Mice, Animals, Inflammasomes, NLR Family, Pyrin Domain-Containing 3 Protein genetics, Amyloid beta-Peptides, Amyloid beta-Protein Precursor genetics, Neuroinflammatory Diseases, Mice, Transgenic, Amyloid, Amyloidogenic Proteins, Alzheimer Disease pathology
- Abstract
Background: Alzheimer's disease (AD) is the most common neurodegenerative disorder affecting memory and cognition. The disease is accompanied by an abnormal deposition of ß-amyloid plaques in the brain that contributes to neurodegeneration and is known to induce glial inflammation. Studies in the APP/PS1 mouse model of ß-amyloid-induced neuropathology have suggested a role for inflammasome activation in ß-amyloid-induced neuroinflammation and neuropathology., Methods: Here, we evaluated the in vivo role of microglia-selective and full body inflammasome signalling in several mouse models of ß-amyloid-induced AD neuropathology., Results: Microglia-specific deletion of the inflammasome regulator A20 and inflammasome effector protease caspase-1 in the App
NL-G-F and APP/PS1 models failed to identify a prominent role for microglial inflammasome signalling in ß-amyloid-induced neuropathology. Moreover, global inflammasome inactivation through respectively full body deletion of caspases 1 and 11 in AppNL-G-F mice and Nlrp3 deletion in APP/PS1 mice also failed to modulate amyloid pathology and disease progression. In agreement, single-cell RNA sequencing did not reveal an important role for Nlrp3 signalling in driving microglial activation and the transition into disease-associated states, both during homeostasis and upon amyloid pathology., Conclusion: Collectively, these results question a generalizable role for inflammasome activation in preclinical amyloid-only models of neuroinflammation., Competing Interests: SD, IP, HM, and AB are employed by Janssen Pharmaceutica NV. ML serves as a consultant for Ventyx Biosciences and Novo Nordisk outside of the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Srinivasan, Kancheva, De Ren, Saito, Jans, Boone, Vandendriessche, Paesmans, Maurin, Vandenbroucke, Hoste, Voet, Scheyltjens, Pavie, Lippens, Schwabenland, Prinz, Saido, Bottelbergs, Movahedi, Lamkanfi and van Loo.)- Published
- 2024
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12. Gut microbiota regulates blood-cerebrospinal fluid barrier function and Aβ pathology.
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Xie J, Bruggeman A, De Nolf C, Vandendriessche C, Van Imschoot G, Van Wonterghem E, Vereecke L, and Vandenbroucke RE
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- Mice, Animals, Blood-Brain Barrier pathology, Amyloid beta-Peptides, Fatty Acids, Volatile, Gastrointestinal Microbiome physiology, Alzheimer Disease pathology, Microbiota
- Abstract
Accumulating evidence indicates that gut microbiota dysbiosis is associated with increased blood-brain barrier (BBB) permeability and contributes to Alzheimer's disease (AD) pathogenesis. In contrast, the influence of gut microbiota on the blood-cerebrospinal fluid (CSF) barrier has not yet been studied. Here, we report that mice lacking gut microbiota display increased blood-CSF barrier permeability associated with disorganized tight junctions (TJs), which can be rescued by recolonization with gut microbiota or supplementation with short-chain fatty acids (SCFAs). Our data reveal that gut microbiota is important not only for the establishment but also for the maintenance of a tight barrier. Also, we report that the vagus nerve plays an important role in this process and that SCFAs can independently tighten the barrier. Administration of SCFAs in App
NL-G-F mice improved the subcellular localization of TJs at the blood-CSF barrier, reduced the β-amyloid (Aβ) burden, and affected microglial phenotype. Altogether, our results suggest that modulating the microbiota and administering SCFAs might have therapeutic potential in AD via blood-CSF barrier tightening and maintaining microglial activity and Aβ clearance., (© 2023 The Authors. Published under the terms of the CC BY 4.0 license.)- Published
- 2023
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13. Free complement and complement containing extracellular vesicles as potential biomarkers for neuroinflammatory and neurodegenerative disorders.
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Burgelman M, Dujardin P, Vandendriessche C, and Vandenbroucke RE
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- Humans, Neuroinflammatory Diseases, Complement System Proteins metabolism, Biomarkers metabolism, Neurodegenerative Diseases diagnosis, Neurodegenerative Diseases metabolism, Extracellular Vesicles metabolism
- Abstract
The complement system is implicated in a broad range of neuroinflammatory disorders such as Alzheimer's disease (AD) and multiple sclerosis (MS). Consequently, measuring complement levels in biofluids could serve as a potential biomarker for these diseases. Indeed, complement levels are shown to be altered in patients compared to controls, and some studies reported a correlation between the level of free complement in biofluids and disease progression, severity or the response to therapeutics. Overall, they are not (yet) suitable as a diagnostic tool due to heterogeneity of reported results. Moreover, measurement of free complement proteins has the disadvantage that information on their origin is lost, which might be of value in a multi-parameter approach for disease prediction and stratification. In light of this, extracellular vesicles (EVs) could provide a platform to improve the diagnostic power of complement proteins. EVs are nanosized double membrane particles that are secreted by essentially every cell type and resemble the (status of the) cell of origin. Interestingly, EVs can contain complement proteins, while the cellular origin can still be determined by the presence of EV surface markers. In this review, we summarize the current knowledge and future opportunities on the use of free and EV-associated complement proteins as biomarkers for neuroinflammatory and neurodegenerative disorders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Burgelman, Dujardin, Vandendriessche and Vandenbroucke.)
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- 2023
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14. Biomarker and therapeutic potential of peripheral extracellular vesicles in Alzheimer's disease.
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Vandendriessche C, Kapogiannis D, and Vandenbroucke RE
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- Biomarkers, Brain, Humans, Neurons, Alzheimer Disease drug therapy, Extracellular Vesicles
- Abstract
Extracellular vesicles (EVs) are cell-derived nanoparticles with an important role in intercellular communication, even across brain barriers. The bidirectional brain-barrier crossing capacity of EVs is supported by research identifying neuronal markers in peripheral EVs, as well as the brain delivery of peripherally administered EVs. In addition, EVs are reflective of their cellular origin, underlining their biomarker and therapeutic potential when released by diseased and regenerative cells, respectively. Both characteristics are of interest in Alzheimer's disease (AD) where the current biomarker profile is solely based on brain-centered readouts and effective therapeutic options are lacking. In this review, we elaborate on the role of peripheral EVs in AD. We focus on bulk EVs and specific EV subpopulations including bacterial EVs (bEVs) and neuronal-derived EVs (nEVs), which have mainly been studied from a biomarker perspective. Furthermore, we highlight the therapeutic potential of peripherally administered EVs whereby research has centered around stem cell derived EVs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)
- Published
- 2022
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15. Characterising extracellular vesicles from individual low volume cerebrospinal fluid samples, isolated by SmartSEC.
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Hirschberg Y, Boonen K, Schildermans K, van Dam A, Pintelon I, Vandendriessche C, Velimirovic M, Jacobs A, Vandenbroucke RE, Nelissen I, Vermeiren Y, and Mertens I
- Abstract
Extracellular vesicles (EVs) are suggested to have a role in the progression of neurodegeneration, and are able to transmit pathological proteins from one cell to another. One of the biofluids from which EVs can be isolated is cerebrospinal fluid (CSF). However, so far, few studies have been performed on small volumes of CSF. Since pooling of patient samples possibly leads to the loss of essential individual patient information, and CSF samples are precious, it is important to have efficient techniques for the isolation of EVs from smaller volumes. In this study, the SmartSEC HT isolation kit from System Biosciences has been evaluated for this purpose. The SmartSEC HT isolation kit was used for isolation of EVs from 500 μL starting volumes of CSF, resulting in two possible EV fractions of 500 μL. Both fractions were characterised and compared to one another using a whole range of characterisation techniques. Results indicated the presence of EVs in both fractions, albeit fraction 1 showed more reproducible results over the different characterisation methods. For example, CMG (CellMask Green membrane stain) fluorescence nanotracking analysis (NTA), ExoView, and the particles/μg ratio demonstrated a clear difference between fraction 1 and 2, where fraction 1 came out as the one where most EVs were eluted with the least contamination. In the other methods, this difference was less noticeable. We successfully performed complementary characterisation tests using only 500 μL of CSF starting volume, and, conclude that fraction 1 consisted of sufficiently pure EVs for further biomarker studies. This means that future EV extractions may be based upon smaller CSF quantities, such as from individual patients. In that way, patient samples do not have to be pooled and individual patient information can be included in forthcoming studies, potentially linking EV content, size and distribution to individualised neurological diagnoses., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Journal of Extracellular Biology published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.)
- Published
- 2022
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16. Special delEVery: Extracellular Vesicles as Promising Delivery Platform to the Brain.
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Pauwels MJ, Vandendriessche C, and Vandenbroucke RE
- Abstract
The treatment of central nervous system (CNS) pathologies is severely hampered by the presence of tightly regulated CNS barriers that restrict drug delivery to the brain. An increasing amount of data suggests that extracellular vesicles (EVs), i.e., membrane derived vesicles that inherently protect and transfer biological cargoes between cells, naturally cross the CNS barriers. Moreover, EVs can be engineered with targeting ligands to obtain enriched tissue targeting and delivery capacities. In this review, we provide a detailed overview of the literature describing a natural and engineered CNS targeting and therapeutic efficiency of different cell type derived EVs. Hereby, we specifically focus on peripheral administration routes in a broad range of CNS diseases. Furthermore, we underline the potential of research aimed at elucidating the vesicular transport mechanisms across the different CNS barriers. Finally, we elaborate on the practical considerations towards the application of EVs as a brain drug delivery system.
- Published
- 2021
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17. Gastric Helicobacter suis Infection Partially Protects against Neurotoxicity in A 6-OHDA Parkinson's Disease Mouse Model.
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Berlamont H, Bruggeman A, Bauwens E, Vandendriessche C, Clarebout E, Xie J, De Bruyckere S, Van Imschoot G, Van Wonterghem E, Ducatelle R, Santens P, Smet A, Haesebrouck F, and Vandenbroucke RE
- Subjects
- Animals, Disease Models, Animal, Dopaminergic Neurons drug effects, Dopaminergic Neurons microbiology, Female, Gliosis chemically induced, Gliosis microbiology, Helicobacter heilmannii growth & development, Inflammation microbiology, Mice, NF-E2-Related Factor 2 genetics, NF-E2-Related Factor 2 metabolism, Neuroprotective Agents, Oxidative Stress physiology, Oxidopamine toxicity, Parkinson Disease complications, Parkinson Disease pathology, Peroxidases genetics, Peroxidases metabolism, Stomach Diseases physiopathology, Helicobacter Infections, Helicobacter heilmannii physiology, Parkinson Disease microbiology, Stomach microbiology
- Abstract
The exact etiology of Parkinson's disease (PD) remains largely unknown, but more and more research suggests the involvement of the gut microbiota. Interestingly, idiopathic PD patients were shown to have at least a 10 times higher prevalence of Helicobacter suis ( H. suis ) DNA in gastric biopsies compared to control patients. H. suis is a zoonotic Helicobacter species that naturally colonizes the stomach of pigs and non-human primates but can be transmitted to humans. Here, we investigated the influence of a gastric H. suis infection on PD disease progression through a 6-hydroxydopamine (6-OHDA) mouse model. Therefore, mice with either a short- or long-term H. suis infection were stereotactically injected with 6-OHDA in the left striatum and sampled one week later. Remarkably, a reduced loss of dopaminergic neurons was seen in the H. suis/ 6-OHDA groups compared to the control/6-OHDA groups. Correspondingly, motor function of the H. suis -infected 6-OHDA mice was superior to that in the non-infected 6-OHDA mice. Interestingly, we also observed higher expression levels of antioxidant genes in brain tissue from H. suis -infected 6-OHDA mice, as a potential explanation for the reduced 6-OHDA-induced cell loss. Our data support an unexpected neuroprotective effect of gastric H. suis on PD pathology, mediated through changes in oxidative stress.
- Published
- 2021
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18. Involvement of the Choroid Plexus in the Pathogenesis of Niemann-Pick Disease Type C.
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Van Hoecke L, Van Cauwenberghe C, Dominko K, Van Imschoot G, Van Wonterghem E, Castelein J, Xie J, Claeys W, Vandendriessche C, Kremer A, Borghgraef P, De Rycke R, Hecimovic S, and Vandenbroucke RE
- Abstract
Niemann-Pick type C (NPC) disease, sometimes called childhood Alzheimer's, is a rare neurovisceral lipid storage disease with progressive neurodegeneration leading to premature death. The disease is caused by loss-of-function mutations in the Npc1 or Npc2 gene which both result into lipid accumulation in the late endosomes and lysosomes. Since the disease presents with a broad heterogenous clinical spectrum, the involved disease mechanisms are still incompletely understood and this hampers finding an effective treatment. As NPC patients, who carry NPC1 mutations, have shown to share several pathological features with Alzheimer's disease (AD) and we and others have previously shown that AD is associated with a dysfunctionality of the blood-cerebrospinal fluid (CSF) barrier located at choroid plexus, we investigated the functionality of this latter barrier in NPC1 pathology. Using NPC1
-/- mice, we show that despite an increase in inflammatory gene expression in choroid plexus epithelial (CPE) cells, the blood-CSF barrier integrity is not dramatically affected. Interestingly, we did observe a massive increase in autophagosomes in CPE cells and enlarged extracellular vesicles (EVs) in CSF upon NPC1 pathology. Additionally, we revealed that these EVs exert toxic effects on brain tissue, in vitro as well as in vivo . Moreover, we observed that EVs derived from the supernatant of NPC1-/- choroid plexus explants are able to induce typical brain pathology characteristics of NPC1-/- , more specifically microgliosis and astrogliosis. Taken together, our data reveal for the first time that the choroid plexus and CSF EVs might play a role in the brain-related pathogenesis of NPC1., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Van Hoecke, Van Cauwenberghe, Dominko, Van Imschoot, Van Wonterghem, Castelein, Xie, Claeys, Vandendriessche, Kremer, Borghgraef, De Rycke, Hecimovic and Vandenbroucke.)- Published
- 2021
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19. Low-grade peripheral inflammation affects brain pathology in the App NL-G-F mouse model of Alzheimer's disease.
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Xie J, Gorlé N, Vandendriessche C, Van Imschoot G, Van Wonterghem E, Van Cauwenberghe C, Parthoens E, Van Hamme E, Lippens S, Van Hoecke L, and Vandenbroucke RE
- Subjects
- Amyloid beta-Protein Precursor, Animals, Brain immunology, Brain pathology, Disease Models, Animal, Female, Male, Mice, Alzheimer Disease immunology, Alzheimer Disease pathology, Inflammation immunology, Inflammation pathology
- Abstract
Alzheimer's disease (AD) is a chronic neurodegenerative disease characterized by the accumulation of amyloid β (Aβ) and neurofibrillary tangles. The last decade, it became increasingly clear that neuroinflammation plays a key role in both the initiation and progression of AD. Moreover, also the presence of peripheral inflammation has been extensively documented. However, it is still ambiguous whether this observed inflammation is cause or consequence of AD pathogenesis. Recently, this has been studied using amyloid precursor protein (APP) overexpression mouse models of AD. However, the findings might be confounded by APP-overexpression artifacts. Here, we investigated the effect of low-grade peripheral inflammation in the APP knock-in (App
NL-G-F ) mouse model. This revealed that low-grade peripheral inflammation affects (1) microglia characteristics, (2) blood-cerebrospinal fluid barrier integrity, (3) peripheral immune cell infiltration and (4) Aβ deposition in the brain. Next, we identified mechanisms that might cause this effect on AD pathology, more precisely Aβ efflux, persistent microglial activation and insufficient Aβ clearance, neuronal dysfunction and promotion of Aβ aggregation. Our results further strengthen the believe that even low-grade peripheral inflammation has detrimental effects on AD progression and may further reinforce the idea to modulate peripheral inflammation as a therapeutic strategy for AD., (© 2021. The Author(s).)- Published
- 2021
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20. Importance of extracellular vesicle secretion at the blood-cerebrospinal fluid interface in the pathogenesis of Alzheimer's disease.
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Vandendriessche C, Balusu S, Van Cauwenberghe C, Brkic M, Pauwels M, Plehiers N, Bruggeman A, Dujardin P, Van Imschoot G, Van Wonterghem E, Hendrix A, Baeke F, De Rycke R, Gevaert K, and Vandenbroucke RE
- Subjects
- Alzheimer Disease genetics, Alzheimer Disease pathology, Amyloid beta-Peptides administration & dosage, Amyloid beta-Peptides toxicity, Animals, Blood-Brain Barrier pathology, Cells, Cultured, Choroid Plexus pathology, Female, Injections, Intraventricular, Mice, Mice, Inbred C57BL, Mice, Transgenic, Alzheimer Disease cerebrospinal fluid, Blood-Brain Barrier metabolism, Choroid Plexus metabolism, Extracellular Vesicles metabolism
- Abstract
Increasing evidence indicates that extracellular vesicles (EVs) play an important role in the pathogenesis of Alzheimer's disease (AD). We previously reported that the blood-cerebrospinal fluid (CSF) interface, formed by the choroid plexus epithelial (CPE) cells, releases an increased amount of EVs into the CSF in response to peripheral inflammation. Here, we studied the importance of CP-mediated EV release in AD pathogenesis. We observed increased EV levels in the CSF of young transgenic APP/PS1 mice which correlated with high amyloid beta (Aβ) CSF levels at this age. The intracerebroventricular (icv) injection of Aβ oligomers (AβO) in wild-type mice revealed a significant increase of EVs in the CSF, signifying that the presence of CSF-AβO is sufficient to induce increased EV secretion. Using in vivo, in vitro and ex vivo approaches, we identified the CP as a major source of the CSF-EVs. Interestingly, AβO-induced, CP-derived EVs induced pro-inflammatory effects in mixed cortical cultures. Proteome analysis of these EVs revealed the presence of several pro-inflammatory proteins, including the complement protein C3. Strikingly, inhibition of EV production using GW4869 resulted in protection against acute AβO-induced cognitive decline. Further research into the underlying mechanisms of this EV secretion might open up novel therapeutic strategies to impact the pathogenesis and progression of AD., (© 2021. The Author(s).)
- Published
- 2021
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21. Extracellular Vesicles: A Double-Edged Sword in Sepsis.
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Burgelman M, Vandendriessche C, and Vandenbroucke RE
- Abstract
Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to an infection. Several studies on mouse and patient sepsis samples have revealed that the level of extracellular vesicles (EVs) in the blood is altered compared to healthy controls, but the different functions of EVs during sepsis pathology are not yet completely understood. Sepsis EVs are described as modulators of inflammation, lymphocyte apoptosis, coagulation and organ dysfunction. Furthermore, EVs can influence clinical outcome and it is suggested that EVs can predict survival. Both detrimental and beneficial roles for EVs have been described in sepsis, depending on the EV cellular source and the disease phase during which the EVs are studied. In this review, we summarize the current knowledge of EV sources and functions during sepsis pathology based on in vitro and mouse models, as well as patient samples.
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- 2021
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22. Extracellular Vesicles in Alzheimer's and Parkinson's Disease: Small Entities with Large Consequences.
- Author
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Vandendriessche C, Bruggeman A, Van Cauwenberghe C, and Vandenbroucke RE
- Subjects
- Exosomes metabolism, Humans, Neurons metabolism, Alzheimer Disease metabolism, Brain metabolism, Extracellular Vesicles metabolism, Parkinson Disease metabolism
- Abstract
Alzheimer's disease (AD) and Parkinson's disease (PD) are incurable, devastating neurodegenerative disorders characterized by the formation and spreading of protein aggregates throughout the brain. Although the exact spreading mechanism is not completely understood, extracellular vesicles (EVs) have been proposed as potential contributors. Indeed, EVs have emerged as potential carriers of disease-associated proteins and are therefore thought to play an important role in disease progression, although some beneficial functions have also been attributed to them. EVs can be isolated from a variety of sources, including biofluids, and the analysis of their content can provide a snapshot of ongoing pathological changes in the brain. This underlines their potential as biomarker candidates which is of specific relevance in AD and PD where symptoms only arise after considerable and irreversible neuronal damage has already occurred. In this review, we discuss the known beneficial and detrimental functions of EVs in AD and PD and we highlight their promising potential to be used as biomarkers in both diseases.
- Published
- 2020
- Full Text
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23. Choroid plexus-derived miR-204 regulates the number of quiescent neural stem cells in the adult brain.
- Author
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Lepko T, Pusch M, Müller T, Schulte D, Ehses J, Kiebler M, Hasler J, Huttner HB, Vandenbroucke RE, Vandendriessche C, Modic M, Martin-Villalba A, Zhao S, LLorens-Bobadilla E, Schneider A, Fischer A, Breunig CT, Stricker SH, Götz M, and Ninkovic J
- Subjects
- Adult, Animals, Cell Cycle, Cell Differentiation, Cell Movement, Female, Gene Expression Regulation, Humans, Male, Mice, MicroRNAs cerebrospinal fluid, Middle Aged, Neural Stem Cells chemistry, Stem Cell Niche, Choroid Plexus chemistry, MicroRNAs genetics, Neural Stem Cells cytology
- Abstract
Regulation of adult neural stem cell (NSC) number is critical for lifelong neurogenesis. Here, we identified a post-transcriptional control mechanism, centered around the microRNA 204 (miR-204), to control the maintenance of quiescent (q)NSCs. miR-204 regulates a spectrum of transcripts involved in cell cycle regulation, neuronal migration, and differentiation in qNSCs. Importantly, inhibition of miR-204 function reduced the number of qNSCs in the subependymal zone (SEZ) by inducing pre-mature activation and differentiation of NSCs without changing their neurogenic potential. Strikingly, we identified the choroid plexus of the mouse lateral ventricle as the major source of miR-204 that is released into the cerebrospinal fluid to control number of NSCs within the SEZ. Taken together, our results describe a novel mechanism to maintain adult somatic stem cells by a niche-specific miRNA repressing activation and differentiation of stem cells., (© 2019 The Authors.)
- Published
- 2019
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24. Long-term organic carbon sequestration in tidal marsh sediments is dominated by old-aged allochthonous inputs in a macrotidal estuary.
- Author
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Van de Broek M, Vandendriessche C, Poppelmonde D, Merckx R, Temmerman S, and Govers G
- Subjects
- Belgium, Biomass, Carbon analysis, Netherlands, Salinity, Time Factors, Carbon Sequestration, Estuaries, Geologic Sediments, Wetlands
- Abstract
Tidal marshes are vegetated coastal ecosystems that are often considered as hotspots of atmospheric CO
2 sequestration. Although large amounts of organic carbon (OC) are indeed being deposited on tidal marshes, there is no direct link between high OC deposition rates and high OC sequestration rates due to two main reasons. First, the deposited OC may become rapidly decomposed once it is buried and, second, a significant part of preserved OC may be allochthonous OC that has been sequestered elsewhere. In this study we aimed to identify the mechanisms controlling long-term OC sequestration in tidal marsh sediments along an estuarine salinity gradient (Scheldt estuary, Belgium and the Netherlands). Analyses of deposited sediments have shown that OC deposited during tidal inundations is up to millennia old. This allochthonous OC is the main component of OC that is effectively preserved in these sediments, as indicated by the low radiocarbon content of buried OC. Furthermore, OC fractionation showed that autochthonous OC is decomposed on a decadal timescale in saltmarsh sediments, while in freshwater marsh sediments locally produced biomass is more efficiently preserved after burial. Our results show that long-term OC sequestration is decoupled from local biomass production in the studied tidal marsh sediments. This implies that OC sequestration rates are greatly overestimated when they are calculated based on short-term OC deposition rates, which are controlled by labile autochthonous OC inputs. Moreover, as allochthonous OC is not sequestered in-situ, it does not contribute to active atmospheric CO2 sequestration in these ecosystems. A correct assessment of the contribution of allochthonous OC to the total sedimentary OC stock in tidal marsh sediments as well as a correct understanding of the long-term fate of locally produced OC are both necessary to avoid overestimations of the rate of in-situ atmospheric CO2 sequestration in tidal marsh sediments., (© 2018 John Wiley & Sons Ltd.)- Published
- 2018
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25. Counteracting the effects of TNF receptor-1 has therapeutic potential in Alzheimer's disease.
- Author
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Steeland S, Gorlé N, Vandendriessche C, Balusu S, Brkic M, Van Cauwenberghe C, Van Imschoot G, Van Wonterghem E, De Rycke R, Kremer A, Lippens S, Stopa E, Johanson CE, Libert C, and Vandenbroucke RE
- Subjects
- Alzheimer Disease genetics, Animals, Cytokines metabolism, Enzyme-Linked Immunosorbent Assay, Female, Immunohistochemistry, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Microscopy, Electron, Scanning, Microscopy, Electron, Transmission, Real-Time Polymerase Chain Reaction, Receptors, Tumor Necrosis Factor, Type I genetics, Alzheimer Disease metabolism, Choroid Plexus cytology, Choroid Plexus metabolism, Receptors, Tumor Necrosis Factor, Type I metabolism
- Abstract
Alzheimer's disease (AD) is the most common form of dementia, and neuroinflammation is an important hallmark of the pathogenesis. Tumor necrosis factor (TNF) might be detrimental in AD, though the results coming from clinical trials on anti-TNF inhibitors are inconclusive. TNFR1, one of the TNF signaling receptors, contributes to the pathogenesis of AD by mediating neuronal cell death. The blood-cerebrospinal fluid (CSF) barrier consists of a monolayer of choroid plexus epithelial (CPE) cells, and AD is associated with changes in CPE cell morphology. Here, we report that TNF is the main inflammatory upstream mediator in choroid plexus tissue in AD patients. This was confirmed in two murine AD models: transgenic APP/PS1 mice and intracerebroventricular (icv) AβO injection. TNFR1 contributes to the morphological damage of CPE cells in AD, and TNFR1 abrogation reduces brain inflammation and prevents blood-CSF barrier impairment. In APP/PS1 transgenic mice, TNFR1 deficiency ameliorated amyloidosis. Ultimately, genetic and pharmacological blockage of TNFR1 rescued from the induced cognitive impairments. Our data indicate that TNFR1 is a promising therapeutic target for AD treatment., (© 2018 The Authors. Published under the terms of the CC BY 4.0 license.)
- Published
- 2018
- Full Text
- View/download PDF
26. Caloric restriction: beneficial effects on brain aging and Alzheimer's disease.
- Author
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Van Cauwenberghe C, Vandendriessche C, Libert C, and Vandenbroucke RE
- Subjects
- Aging pathology, Alzheimer Disease physiopathology, Biomimetics, Brain drug effects, Energy Metabolism genetics, Humans, Resveratrol, Sirolimus therapeutic use, Stilbenes therapeutic use, Aging metabolism, Alzheimer Disease diet therapy, Brain physiopathology, Caloric Restriction
- Abstract
Dietary interventions such as caloric restriction (CR) extend lifespan and health span. Recent data from animal and human studies indicate that CR slows down the aging process, benefits general health, and improves memory performance. Caloric restriction also retards and slows down the progression of different age-related diseases, such as Alzheimer's disease. However, the specific molecular basis of these effects remains unclear. A better understanding of the pathways underlying these effects could pave the way to novel preventive or therapeutic strategies. In this review, we will discuss the mechanisms and effects of CR on aging and Alzheimer's disease. A potential alternative to CR as a lifestyle modification is the use of CR mimetics. These compounds mimic the biochemical and functional effects of CR without the need to reduce energy intake. We discuss the effect of two of the most investigated mimetics, resveratrol and rapamycin, on aging and their potential as Alzheimer's disease therapeutics. However, additional research will be needed to determine the safety, efficacy, and usability of CR and its mimetics before a general recommendation can be proposed to implement them.
- Published
- 2016
- Full Text
- View/download PDF
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