PUBLICATION
An Antagonistic Axon-Dendrite Interplay Enables Efficient Neuronal Repair in the Adult Zebrafish Central Nervous System
- Authors
- Beckers, A., Van Dyck, A., Bollaerts, I., Van Houcke, J., Lefevere, E., Andries, L., Agostinone, J., Van Hove, I., Di Polo, A., Lemmens, K., Moons, L.
- ID
- ZDB-PUB-180816-8
- Date
- 2018
- Source
- Molecular neurobiology 56(5): 3175-3192 (Journal)
- Registered Authors
- Keywords
- Axonal regeneration, Dendritic remodeling, Optic nerve crush, Retina, Zebrafish, mTOR and MMP inhibitor studies
- MeSH Terms
-
- Animals
- Axons/drug effects
- Axons/metabolism*
- Central Nervous System/physiology*
- Dendrites/drug effects
- Dendrites/metabolism*
- Matrix Metalloproteinase Inhibitors/pharmacology
- Nerve Crush
- Nerve Regeneration*/drug effects
- Optic Nerve Injuries/pathology
- Optic Nerve Injuries/physiopathology
- Retinal Ganglion Cells/drug effects
- Retinal Ganglion Cells/pathology
- TOR Serine-Threonine Kinases/antagonists & inhibitors
- TOR Serine-Threonine Kinases/metabolism
- Zebrafish/physiology*
- PubMed
- 30105671 Full text @ Mol. Neurobiol.
Citation
Beckers, A., Van Dyck, A., Bollaerts, I., Van Houcke, J., Lefevere, E., Andries, L., Agostinone, J., Van Hove, I., Di Polo, A., Lemmens, K., Moons, L. (2018) An Antagonistic Axon-Dendrite Interplay Enables Efficient Neuronal Repair in the Adult Zebrafish Central Nervous System. Molecular neurobiology. 56(5):3175-3192.
Abstract
Neural insults and neurodegenerative diseases typically result in permanent functional deficits, making the identification of novel pro-regenerative molecules and mechanisms a primary research topic. Nowadays, neuroregenerative research largely focuses on improving axonal regrowth, leaving the regenerative properties of dendrites largely unstudied. Moreover, whereas developmental studies indicate a strict temporal separation of axogenesis and dendritogenesis and thus suggest a potential interdependency of axonal and dendritic outgrowth, a possible axon-dendrite interaction during regeneration remains unexplored. To unravel the inherent dendritic response of vertebrate neurons undergoing successful axonal regeneration, regeneration-competent adult zebrafish of either sex, subjected to optic nerve crush (ONC), were used. A longitudinal study in which retinal ganglion cell (RGC) dendritic remodeling and axonal regrowth were assessed side-by-side after ONC, revealed that-as during development-RGC axogenesis precedes dendritogenesis during central nervous system (CNS) repair. Moreover, dendrites majorly shrank before the start of axonal regrowth and were only triggered to regrow upon RGC target contact initiation, altogether suggestive for a counteractive interplay between axons and dendrites after neuronal injury. Strikingly, both retinal mechanistic target of rapamycin (mTOR) and broad-spectrum matrix metalloproteinase (MMP) inhibition after ONC consecutively inhibited RGC synapto-dendritic deterioration and axonal regrowth, thus invigorating an antagonistic interplay wherein mature dendrites restrain axonal regrowth. Altogether, this work launches dendritic shrinkage as a prerequisite for efficient axonal regrowth of adult vertebrate neurons, and indicates that molecular/mechanistic analysis of dendritic responses after damage might represent a powerful target-discovery platform for neural repair.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping