MMP-2 as a modulator of dendritic shrinkage and axonal regeneration: neuroinflammation as the driving force

Abstract

Event Abstract Back to Event MMP-2 as a modulator of dendritic shrinkage and axonal regeneration: neuroinflammation as the driving force Lien Andries1*, Manuel Salinas Navarro1, Kim Lemmens1, Lies De Groef1 and Lieve Moons1 1 KU Leuven, Biology, Belgium A limited number of experiments performed across the animal kingdom hints to improved axonal regeneration upon stimulation of dendritic shrinkage in adult injured neurons. In this study, we use the visual system as a model to investigate dendrite remodeling and axonal regeneration following injury. Damage to the adult mammalian optic nerve, along which the retinal ganglion cells (RGCs) project their axons, is characterized by axonal degeneration, shrinkage of the dendrites in the inner plexiform layer (IPL) of the retina and eventually RGC death. Notably, inflammatory stimulation (IS) within the retina has been suggested to transform the RGCs into an active regenerative state. Several players essential to this regeneration-promoting effect of IS have been identified. However, our understanding of the multiple glial- or macrophage-derived factors that may synergistically contribute or potentiate the beneficial effects of IS, is still incomplete. Here, we propose MMP-2 as one of the modulators of dendritic and axonal responses after optic nerve crush (ONC) (degeneration model) or ONC combined with IS (regeneration model). Besides the well-known axonal regeneration promoting effect of IS, our data now suggest that IS also affects dendritic shrinkage. This was assessed by measuring the thickness of the IPL using optical coherence tomography (OCT) and (immuno)histological stainings on retinal sections. Wild type (WT) mice subjected to ONC+IS showed increased IPL thinning as compared to mice subjected to ONC solely. Furthermore, MMP-2 seems to exert a role in both dendritic and axonal processes. On the one hand, Mmp-2-/- mice were characterized by a delayed IPL thinning: at 4 and 7dpi, wild-type (WT) mice already show significant IPL thinning, while this is not the case for Mmp-2-/- mice. On the other hand, axonal regeneration was assessed by quantifying fluorescently labelled cholera toxin beta (CTB-alexa 488)-positive axons in optic nerve sections. Mmp-2-/- mice show less axonal regeneration in the optic nerve. A significant lower number of CTB+ regenerating axons was found in Mmp-2-/- mice versus WT mice. Notably, after ONC+IS, Müller glia and infiltrating immune cells were identified as the major producers of MMP-2. Bone marrow transplantations, FACS and cytokine profiling are currently ongoing to unravel the downstream cellular and molecular players. Taken together, MMP-2 plays a beneficial role during axonal regeneration and affects both dendritic and axonal compartments. Furthermore, MMP-2 expression by invading immune cells puts MMP-2 forward as a molecule linking IS to enhanced axonal regeneration. Our results suggest that the underlying mechanism of neuroinflammatory-induced axonal regeneration might partially reside in an increased potential to promote dendritic retraction, yet, more research is needed to investigate the link between dendritic shrinkage and axonal regeneration. Keywords: MMP-2, Neuroinflammation, Optic Nerve Injuries, axonal regeneration, dendrite remodeling Conference: 12th National Congress of the Belgian Society for Neuroscience, Gent, Belgium, 22 May - 22 May, 2017. Presentation Type: Oral Presentation Topic: Disorders of the Nervous System Citation: Andries L, Salinas Navarro M, Lemmens K, De Groef L and Moons L (2019). MMP-2 as a modulator of dendritic shrinkage and axonal regeneration: neuroinflammation as the driving force. Front. Neurosci. Conference Abstract: 12th National Congress of the Belgian Society for Neuroscience. doi: 10.3389/conf.fnins.2017.94.00091 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 21 Apr 2017; Published Online: 25 Jan 2019. * Correspondence: Miss. Lien Andries, KU Leuven, Biology, Leuven, 3000, Belgium, lien.andries@kuleuven.be Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Lien Andries Manuel Salinas Navarro Kim Lemmens Lies De Groef Lieve Moons Google Lien Andries Manuel Salinas Navarro Kim Lemmens Lies De Groef Lieve Moons Google Scholar Lien Andries Manuel Salinas Navarro Kim Lemmens Lies De Groef Lieve Moons PubMed Lien Andries Manuel Salinas Navarro Kim Lemmens Lies De Groef Lieve Moons Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.