14 results on '"Moons, Lieve"'
Search Results
2. Complementary research models and methods to study axonal regeneration in the vertebrate retinofugal system
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Bollaerts, Ilse, Veys, Lien, Geeraerts, Emiel, Andries, Lien, De Groef, Lies, Buyens, Tom, Salinas-Navarro, Manuel, Moons, Lieve, and Van Hove, Inge
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- 2018
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3. Matrix Metalloproteinases During Axonal Regeneration, a Multifactorial Role from Start to Finish
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Andries, Lien, Van Hove, Inge, Moons, Lieve, and De Groef, Lies
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- 2017
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4. A new microfluidic model to study dendritic remodeling and mitochondrial dynamics during axonal regeneration of adult zebrafish retinal neurons.
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Van Dyck, Annelies, Masin, Luca, Bergmans, Steven, Schevenels, Giel, Beckers, An, Vanhollebeke, Benoit, and Moons, Lieve
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NERVOUS system regeneration ,OPTIC nerve injuries ,BRACHYDANIO ,RETINAL ganglion cells ,CENTRAL nervous system ,DENDRITIC spines ,OLIGODENDROGLIA - Abstract
Unlike mammals, adult zebrafish are able to fully regenerate axons and functionally recover from neuronal damage in the mature central nervous system (CNS). Decades of research have tried to identify the mechanisms behind their spontaneous regenerative capacity, but the exact underlying pathways and molecular drivers remain to be fully elucidated. By studying optic nerve injury-induced axonal regrowth of adult zebrafish retinal ganglion cells (RGCs), we previously reported transient dendritic shrinkage and changes in the distribution and morphology of mitochondria in the different neuronal compartments throughout the regenerative process. These data suggest that dendrite remodeling and temporary changes in mitochondrial dynamics contribute to effective axonal and dendritic repair upon optic nerve injury. To further elucidate these interactions, we here present a novel adult zebrafish microfluidic model in which we can demonstrate compartment-specific alterations in resource allocation in real-time at single neuron level. First, we developed a pioneering method that enables to isolate and culture adult zebrafish retinal neurons in a microfluidic setup. Notably, with this protocol, we report on a long-term adult primary neuronal culture with a high number of surviving and spontaneously outgrowing mature neurons, which was thus far only very limitedly described in literature. By performing timelapse live cell imaging and kymographic analyses in this setup, we can explore changes in dendritic remodeling and mitochondrial motility during spontaneous axonal regeneration. This innovative model system will enable to discover how redirecting intraneuronal energy resources supports successful regeneration in the adult zebrafish CNS, and might facilitate the discovery of new therapeutic targets to promote neuronal repair in humans. [ABSTRACT FROM AUTHOR]
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- 2023
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5. Optic nerve injury-induced regeneration in the adult zebrafish is accompanied by spatiotemporal changes in mitochondrial dynamics.
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An Beckers, An Beckers, Masin, Luca, Van Dyck, Annelies, Bergmans, Steven, Vanhunsel, Sophie, Zhang, Anyi, Verreet, Tine, Poulain, Fabienne E., Farrow, Karl, and Moons, Lieve
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- 2023
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6. The age factor in optic nerve regeneration: Intrinsic and extrinsic barriers hinder successful recovery in the short‐living killifish.
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Vanhunsel, Sophie, Bergmans, Steven, Beckers, An, Etienne, Isabelle, Van Bergen, Tine, De Groef, Lies, and Moons, Lieve
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OPTIC nerve ,NERVOUS system regeneration ,KILLIFISHES ,CENTRAL nervous system ,CENTRAL nervous system diseases - Abstract
As the mammalian central nervous system matures, its regenerative ability decreases, leading to incomplete or non‐recovery from the neurodegenerative diseases and central nervous system insults that we are increasingly facing in our aging world population. Current neuroregenerative research is largely directed toward identifying the molecular and cellular players that underlie central nervous system repair, yet it repeatedly ignores the aging context in which many of these diseases appear. Using an optic nerve crush model in a novel biogerontology model, that is, the short‐living African turquoise killifish, the impact of aging on injury‐induced optic nerve repair was investigated. This work reveals an age‐related decline in axonal regeneration in female killifish, with different phases of the repair process being affected depending on the age. Interestingly, as in mammals, both a reduced intrinsic growth potential and a non‐supportive cellular environment seem to lie at the basis of this impairment. Overall, we introduce the killifish visual system and its age‐dependent regenerative ability as a model to identify new targets for neurorepair in non‐regenerating individuals, thereby also considering the effects of aging on neurorepair. [ABSTRACT FROM AUTHOR]
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- 2022
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7. Neuroinflammation and Optic Nerve Regeneration: Where Do We Stand in Elucidating Underlying Cellular and Molecular Players?
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Andries, Lien, De Groef, Lies, and Moons, Lieve
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NERVOUS system regeneration ,OPTIC nerve ,INFLAMMATION ,CENTRAL nervous system diseases ,CELLULAR control mechanisms - Abstract
Neurodegenerative diseases and central nervous system (CNS) trauma are highly irreversible, in part because adult mammals lack a robust regenerative capacity. A multifactorial problem underlies the limited axonal regeneration potential. Strikingly, neuroinflammation seems able to induce axonal regrowth in the adult mammalian CNS. It is increasingly clear that both blood-borne and resident inflammatory cells as well as reactivated glial cells affect axonal regeneration. The scope of this review is to give a comprehensive overview of the knowledge that links inflammation (with a focus on the innate immune system) to axonal regeneration and to critically reflect on the controversy that still prevails about the cells, molecules and pathways that are dominating the scene. Also, a brief overview is given of what is already known about the crosstalk between and the heterogeneity of cell types that might play a role in axonal regeneration. Recent research indicates that inflammation-induced axonal regrowth is not solely driven by a single-cell population but probably relies on the crosstalk between multiple cell types and the strong regulation of these cell populations in time and space. Moreover, there is growing evidence that the different cell populations are highly heterogeneous and as such can react differently upon injury. This could explain the controversial results that have been obtained over the past years. The primary focus of this manuscript is the retinofugal system of adult mammals, however, when relevant, insights or examples of the spontaneous regenerating zebrafish model and spinal cord research are added. [ABSTRACT FROM AUTHOR]
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- 2020
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8. Matrix metalloproteinases as promising regulators of axonal regrowth in the injured adult zebrafish retinotectal system
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Lemmens, Kim, Bollaerts, Ilse, Bhumika, Stitipragyan, De Groef, Lies, Van houcke, Jessie, Darras, Veerle, Van Hove, Inge, and Moons, Lieve
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Analysis of Variance ,Nerve Crush ,Neuronal Outgrowth ,matrix metalloproteinases ,axonal regeneration ,Dipeptides ,Matrix Metalloproteinase Inhibitors ,zebrafish ,optic nerve injury ,Gene Expression Regulation, Enzymologic ,Nerve Regeneration ,Disease Models, Animal ,nervous system ,Tubulin ,Optic Nerve Diseases ,Animals ,Visual Pathways ,sense organs - Abstract
Overcoming the failure of axon regeneration in the mammalian central nervous system (CNS) after injury remains a major challenge, which makes the search for proregenerative molecules essential. Matrix metalloproteinases (MMPs) have been implicated in axonal outgrowth during CNS development and show increased expression levels during vertebrate CNS repair. In mammals, MMPs are believed to alter the suppressive extracellular matrix to become more permissive for axon regrowth. We investigated the role of MMPs in axonal regeneration following optic nerve crush (ONC) in adult zebrafish, which fully recover from such injuries due to a high intrinsic axon growth capacity and a less inhibitory environment. Lowering general retinal MMP activity through intravitreal injections of GM6001 after ONC strongly reduced retinal ganglion cell (RGC) axonal regrowth, without influencing RGC survival. Based on a recently performed transcriptome profiling study, the expression pattern of four MMPs after ONC was determined via combined use of western blotting and immunostainings. Mmp-2 and -13a were increasingly present in RGC somata during axonal regrowth. Moreover, Mmp-2 and -9 became upregulated in regrowing RGC axons and inner plexiform layer (IPL) synapses, respectively. In contrast, after an initial rise in IPL neurites and RGC axons during the injury response, Mmp-14 expression decreased during regeneration. Altogether, a phase-dependent expression pattern for each specific MMP was observed, implicating them in axonal regrowth and inner retina remodeling after injury. In conclusion, these data suggest a novel, neuron-intrinsic function for multiple MMPs in axon regrowth that is distinct from breaking down environmental barriers. J. Comp. Neurol. 524:1472-1493, 2016. © 2015 Wiley Periodicals, Inc. ispartof: Journal of Comparative Neurology vol:524 issue:7 pages:1472-1493 ispartof: location:United States status: published
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- 2016
9. Automated Analysis of Neurite Outgrowth in Mouse Retinal Explants.
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Gaublomme, Djoere, Buyens, Tom, and Moons, Lieve
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AXONS ,REGENERATION (Biology) ,CENTRAL nervous system ,NEUROGLIA ,NEURAL stimulation ,NEURONS - Abstract
Despite intensive research efforts over the past years, regeneration of injured axons in the central nervous system remains elusive. In the quest for neurostimulatory agents that promote regeneration, well-defined models and analysis methods are required. Tissue explant cultures closely resemble the in vivo situation, making them ideal to study the effect of compounds on the neuro-glial network. This study reports the optimization of an explant culture technique using retinas of neonatal mice and the development of an analysis script that allows for rapid and automated analysis of neurite outgrowth from these explants. The key features of this script (i.e., local thresholding and form selection) allow for swift and unbiased detection of neurite outgrowth. The novel analysis method is compared with two commonly used manual methods and successfully validated by performing dose-response studies with molecules known to either inhibit (anti–β1-integrin antibody) or stimulate (brain-derived neurotrophic factor and ciliary neurotrophic factor) neurite outgrowth from retinal explants. Finally, the new analysis script is used to study whether retinal explant origin has any effect on neurite outgrowth. [ABSTRACT FROM PUBLISHER]
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- 2013
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10. MMP2 Modulates Inflammatory Response during Axonal Regeneration in the Murine Visual System.
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Andries, Lien, Masin, Luca, Navarro, Manuel Salinas, Zaunz, Samantha, Claes, Marie, Bergmans, Steven, Brouwers, Véronique, Lefevere, Evy, Verfaillie, Catherine, Movahedi, Kiavash, De Groef, Lies, and Moons, Lieve
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NERVOUS system regeneration ,AXONS ,MYELOID cells ,INFLAMMATION ,BONE marrow transplantation ,LABORATORY mice - Abstract
Neuroinflammation has been put forward as a mechanism triggering axonal regrowth in the mammalian central nervous system (CNS), yet little is known about the underlying cellular and molecular players connecting these two processes. In this study, we provide evidence that MMP2 is an essential factor linking inflammation to axonal regeneration by using an in vivo mouse model of inflammation-induced axonal regeneration in the optic nerve. We show that infiltrating myeloid cells abundantly express MMP2 and that MMP2 deficiency results in reduced long-distance axonal regeneration. However, this phenotype can be rescued by restoring MMP2 expression in myeloid cells via a heterologous bone marrow transplantation. Furthermore, while MMP2 deficiency does not affect the number of infiltrating myeloid cells, it does determine the coordinated expression of pro- and anti-inflammatory molecules. Altogether, in addition to its role in axonal regeneration via resolution of the glial scar, here, we reveal a new mechanism via which MMP2 facilitates axonal regeneration, namely orchestrating the expression of pro- and anti-inflammatory molecules by infiltrating innate immune cells. [ABSTRACT FROM AUTHOR]
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- 2021
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11. One Raft to Guide Them All, and in Axon Regeneration Inhibit Them.
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Hernaiz-Llorens, Marc, Martínez-Mármol, Ramón, Roselló-Busquets, Cristina, Soriano, Eduardo, and Moons, Lieve
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NERVOUS system regeneration ,AXONS ,CENTRAL nervous system ,LIPID rafts ,NEURAL circuitry ,CHONDROITIN sulfate proteoglycan ,NERVOUS system ,MEMBRANE lipids - Abstract
Central nervous system damage caused by traumatic injuries, iatrogenicity due to surgical interventions, stroke and neurodegenerative diseases is one of the most prevalent reasons for physical disability worldwide. During development, axons must elongate from the neuronal cell body to contact their precise target cell and establish functional connections. However, the capacity of the adult nervous system to restore its functionality after injury is limited. Given the inefficacy of the nervous system to heal and regenerate after damage, new therapies are under investigation to enhance axonal regeneration. Axon guidance cues and receptors, as well as the molecular machinery activated after nervous system damage, are organized into lipid raft microdomains, a term typically used to describe nanoscale membrane domains enriched in cholesterol and glycosphingolipids that act as signaling platforms for certain transmembrane proteins. Here, we systematically review the most recent findings that link the stability of lipid rafts and their composition with the capacity of axons to regenerate and rebuild functional neural circuits after damage. [ABSTRACT FROM AUTHOR]
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- 2021
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12. Injury-induced Autophagy Delays Axonal Regeneration after Optic Nerve Damage in Adult Zebrafish.
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Beckers, An, Vanhunsel, Sophie, Van Dyck, Annelies, Bergmans, Steven, Masin, Luca, and Moons, Lieve
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NERVOUS system regeneration , *OPTIC nerve , *AUTOPHAGY , *RETINAL ganglion cells , *CENTRAL nervous system , *OPTIC nerve injuries - Abstract
• ONC triggers autophagy in the retinotectal system of adult zebrafish. • Injured RGCs induce autophagy in their soma and regrowing axons. • Macroglial cells in the optic nerve/optic tectum display autophagy after ONC. • Systemic autophagy inhibition accelerates axonal regeneration. • Increased mTOR activity might underlie the positive effect of autophagy inhibition. Optic neuropathies comprise a group of disorders in which the axons of retinal ganglion cells (RGCs), the retinal projection neurons conveying visual information to the brain, are damaged. This results in visual impairment or even blindness, which is irreversible as adult mammals lack the capacity to repair or replace injured or lost neurons. Despite intensive research, no efficient treatment to induce axonal regeneration in the central nervous system (CNS) is available yet. Autophagy, the cellular recycling response, was shown repeatedly to be elevated in animal models of optic nerve injury, and both beneficial and detrimental effects have been reported. In this study, we subjected spontaneously regenerating adult zebrafish to optic nerve damage (ONC) and revealed that autophagy is enhanced after optic nerve damage in zebrafish, both in RGC axons and somas, as well as in macroglial cells of the retina, the optic nerve and the visual target areas in the brain. Interestingly, the pattern of the autophagic response in the axons followed the spatiotemporal window of axonal regrowth, which suggests that autophagy is ongoing at the growth cones. Pharmacological inhibition of the recycling pathway resulted in accelerated RGC target reinnervation, possibly linked to increased mechanistic target of rapamycin (mTOR) activity, known to stimulate axonal regrowth. Taken together, these intriguing findings underline that further research is warranted to decipher if modulation of autophagy could be an effective therapeutic method to induce CNS regeneration. [ABSTRACT FROM AUTHOR]
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- 2021
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13. Successful optic nerve regeneration in the senescent zebrafish despite age-related decline of cell intrinsic and extrinsic response processes.
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Van houcke, Jessie, Bollaerts, Ilse, Geeraerts, Emiel, Davis, Benjamin, Beckers, An, Van Hove, Inge, Lemmens, Kim, De Groef, Lies, and Moons, Lieve
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OPTIC nerve diseases , *NEURODEGENERATION , *ALEXANDER disease , *DEGENERATION (Pathology) , *SCHINZEL-Giedion syndrome - Abstract
Dysfunction of the central nervous system (CNS) in neurodegenerative diseases or after brain lesions seriously affects life quality of a growing number of elderly, since the adult CNS lacks the capacity to replace or repair damaged neurons. Despite intensive research efforts, full functional recovery after CNS disease and/or injury remains challenging, especially in an aging environment. As such, there is a rising need for an aging model in which the impact of aging on successful regeneration can be studied. Here, we introduce the senescent zebrafish retinotectal system as a valuable model to elucidate the cellular and molecular processes underlying age-related decline in axonal regeneration capacities. We found both intrinsic and extrinsic response processes to be altered in aged fish. Indeed, expression levels of growth-associated genes are reduced in naive and crushed retinas, and the injury-associated increase in innate immune cell density appears delayed, suggesting retinal inflammaging in old fish. Strikingly, however, despite a clear deceleration in regeneration onset and early axon outgrowth leading to an overall slowing of optic nerve regeneration, reinnervation of the optic tectum and recovery of visual function occurs successfully in the aged zebrafish retinotectal system. [ABSTRACT FROM AUTHOR]
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- 2017
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14. Towards axonal regeneration and neuroprotection in glaucoma: Rho kinase inhibitors as promising therapeutics.
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Van de Velde, Sarah, De Groef, Lies, Stalmans, Ingeborg, Moons, Lieve, and Van Hove, Inge
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NERVOUS system regeneration , *TREATMENT of neurodegeneration , *GLAUCOMA , *NEUROPROTECTIVE agents , *AXONS , *BLINDNESS , *RHO-associated kinases , *PATIENTS , *DISEASE risk factors - Abstract
Due to a prolonged life expectancy worldwide, the incidence of age-related neurodegenerative disorders such as glaucoma is increasing. Glaucoma is the second cause of blindness, resulting from a slow and progressive loss of retinal ganglion cells (RGCs) and their axons. Up to now, intraocular pressure (IOP) reduction is the only treatment modality by which ophthalmologists attempt to control disease progression. However, not all patients benefit from this therapy, and the pathophysiology of glaucoma is not always associated with an elevated IOP. These limitations, together with the multifactorial etiology of glaucoma, urge the pressing medical need for novel and alternative treatment strategies. Such new therapies should focus on preventing or retarding RGC death, but also on repair of injured axons, to ultimately preserve or improve structural and functional connectivity. In this respect, Rho-associated coiled-coil forming protein kinase (ROCK) inhibitors hold a promising potential to become very prominent drugs for future glaucoma treatment. Their field of action in the eye does not seem to be restricted to IOP reduction by targeting the trabecular meshwork or improving filtration surgery outcome. Indeed, over the past years, important progress has been made in elucidating their ability to improve ocular blood flow, to prevent RGC death/increase RGC survival and to retard axonal degeneration or induce proper axonal regeneration. Within this review, we aim to highlight the currently known capacity of ROCK inhibition to promote neuroprotection and regeneration in several in vitro , ex vivo and in vivo experimental glaucoma models. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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