Axon and dendrite regrowth are temporally correlated upon injury in the CNS of adult zebrafish

Event Abstract Back to Event Axon and dendrite regrowth are temporally correlated upon injury in the CNS of adult zebrafish An Beckers1*, Ilse Bollaerts1, Jessie Van Houcke1, Kim Lemmens1 and Lieve Moons1 1 KU Leuven, Biology, Belgium Purpose: Despite intensive research, successful regeneration and subsequent functional recovery of the injured or diseased mammalian central nervous system (CNS) can still not be evoked. However, one essential component of the neuronal circuitry might have been overlooked for decades: the dendrites. Dendritic remodeling is well studied during development of the retinofugal system, in which there is a distinct and ordered temporal window for axonal versus dendritic outgrowth with axogenesis preceding dendritogenesis. Whether this interplay between axon and dendrite regeneration also occurs in adult injured neurons remains unknown, but defects in dendritic arborization and connectivity are recognized as one of the first stages of retinal neurodegeneration, such as in glaucoma. This immediate retraction of dendrites after optic nerve damage might reflect an attempt to repeat the ordered developmental program in adult organisms, in which axogenesis precedes dendritogenesis. As axonal regeneration cannot yet be induced successfully in mammals, we investigated this intriguing hypothesis in the spontaneously regenerating zebrafish, which is considered an ideal model organism to identify mechanisms underlying CNS repair. We applied the optic nerve crush (ONC) model to map synaptic and dendrite responses of inner retinal neurons during axonal regeneration in adult zebrafish. Methods: Axonal regeneration was characterized using retinal GAP-43 expression, determined via western blotting (WB) and immunohistochemistry (IHC). Next, biocytin labeling was employed to map optic tectum reinnervation. Dendritic remodeling, in contrast, was studied via morphometric analysis of inner plexiform layer (IPL) thickness on H&E stained retinal sections and by protein quantification of dendrite (MAP2) and synapse (SV2) markers via WB. The removal/reoccurrence of synaptic contacts in the optic tectum and retina was studied via IHC with the synaptic markers znp-1 and PSD95, respectively. Finally, primary functional recovery was determined with the dorsal light reflex test. Results: In naive fish, GAP-43 was mainly expressed in RGC dendrites, suggestive of a continuous synaptic shifting or dendritic growth. At 4 days post injury (dpi), GAP-43 expression was highly upregulated in RGC somata and axons, but diminished in the IPL, indicative for, respectively, axonal regeneration and dendrite retraction. A significant decrease in IPL thickness and MAP2 and SV2 expression at 4 dpi also indicated dendrite retraction. In addition, the number of synaptic contacts in the IPL was also declined, as shown by a reduction in PSD95-positive punctae. On the other hand, optic tectum reinnervation was fully ongoing at 4 and 7 dpi and was completed at 14 dpi. Synaptic contacts in the optic tectum were restored from 14 dpi onwards, as show via IHC for znp-1. Notably, from 7-14 dpi, the GAP-43 fluorescent signal reappeared in IPL dendrites, IPL thickness was restored and more PSD95 positive punctae reappeared. Furthermore, also MAP2 and SV2 expression was fully recovered at 14 dpi. All these data thus indicate dendritic repair, and as a result, primary visual recovery was found to be established at 18 dpi. Conclusion: Similar to mammals, optic nerve injury induces synaptic degeneration and dendrite shrinkage in the retina of zebrafish. This dendrite retraction occurs during the RGC axonal regrowth phase. Furthermore, upon RGC target reinnervation, RGC dendrites of zebrafish appear able to regain their morphology and synaptic connectivity. These data suggest that injured RGCs in adult zebrafish recapitulate development, where RGCs first show an axonal growth mode, followed by dendrite maturation. Keywords: Zebrafish, Regeneration, Dendrites, Axons, Neurons 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: Beckers A, Bollaerts I, Van Houcke J, Lemmens K and Moons L (2019). Axon and dendrite regrowth are temporally correlated upon injury in the CNS of adult zebrafish. Front. Neurosci. Conference Abstract: 12th National Congress of the Belgian Society for Neuroscience. doi: 10.3389/conf.fnins.2017.94.00098 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. An Beckers, KU Leuven, Biology, Leuven, 3000, Belgium, an_beckers@hotmail.com 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 An Beckers Ilse Bollaerts Jessie Van Houcke Kim Lemmens Lieve Moons Google An Beckers Ilse Bollaerts Jessie Van Houcke Kim Lemmens Lieve Moons Google Scholar An Beckers Ilse Bollaerts Jessie Van Houcke Kim Lemmens Lieve Moons PubMed An Beckers Ilse Bollaerts Jessie Van Houcke Kim Lemmens 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.