June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Intraneuronal energy reshuffling by mitochondrial dynamics drives injury-induced axonal regeneration in adult zebrafish
Author Affiliations & Notes
  • An Beckers
    Biology, Katholieke Universiteit Leuven, Leuven, Flanders, Belgium
  • Annelies Van Dyck
    Biology, Katholieke Universiteit Leuven, Leuven, Flanders, Belgium
  • Luca Masin
    Biology, Katholieke Universiteit Leuven, Leuven, Flanders, Belgium
  • Steven Bergmans
    Biology, Katholieke Universiteit Leuven, Leuven, Flanders, Belgium
  • Lien Andries
    Biology, Katholieke Universiteit Leuven, Leuven, Flanders, Belgium
  • Lies De Groef
    Biology, Katholieke Universiteit Leuven, Leuven, Flanders, Belgium
  • Lieve K M Moons
    Biology, Katholieke Universiteit Leuven, Leuven, Flanders, Belgium
  • Footnotes
    Commercial Relationships   An Beckers, None; Annelies Van Dyck, None; Luca Masin, None; Steven Bergmans, None; Lien Andries, None; Lies De Groef, None; Lieve Moons, None
  • Footnotes
    Support  Research grant Fonds Wetenschappelijk Onderzoek
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 3037. doi:
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      An Beckers, Annelies Van Dyck, Luca Masin, Steven Bergmans, Lien Andries, Lies De Groef, Lieve K M Moons; Intraneuronal energy reshuffling by mitochondrial dynamics drives injury-induced axonal regeneration in adult zebrafish. Invest. Ophthalmol. Vis. Sci. 2021;62(8):3037.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Neuroregenerative research largely focuses on improving axonal regrowth, leaving dendrites mostly unstudied, despite their importance for neural circuit functioning. We previously determined the dendritic response of retinal ganglion cells (RGCs) during axonal outgrowth after optic nerve crush (ONC) in regeneration-competent adult zebrafish and revealed an antagonistic axon-dendrite interplay, wherein early dendritic retraction boosts axonal regrowth and RGC dendrites only regenerate after target innervation in the brain. One underlying mechanism might be an intraneuronal energy trade-off that prevents simultaneous axonal regrowth and maintenance/regrowth of dendrites. To test this idea, we focused on mitochondria, increasingly recognized to exert a critical role in axonal regeneration.

Methods : The mitochondrial distribution within RGC dendrites, axons and somas was characterized at several time points after ONC, using retinal flat mounts of mitochondrial reporter fish and a Python script. Cryosections were used to localize the mitochondria inside the optic nerve and optic tectum. To study mitochondrial dynamic changes upon injury, IHC and WB for biogenesis, fission, fusion and mitophagy markers were used.

Results : Early after ONC, mitochondrial numbers strongly decreased in the RGC dendrites as well as in their axonal projection areas in the optic tectum, concomitant with dendrite retraction and axonal degeneration in retina and tectum, respectively. Mitochondria re-appeared first in tectal RGC axons at the moment of reinnervation and in the RGC dendrites upon their repair. Regarding mitochondrial dynamics, a biphasic upregulation of biogenesis was found, respectively before the start of axon/dendrite regrowth, suggesting a role of the new mitochondria within these processes. While the level of fusion remained unchanged during the complete regenerative process, fission was strongly increased after ONC during dendritic retraction and axonal regrowth, as well as mitophagy.

Conclusions : The timed dendrite-axon-dendrite mitochondrial translocation after ONC fits the hypothesis that dendritic mitochondria reshuffle energy to the axons to boost repair, and that dendrite regrowth is aided by a return of mitochondria to the retina. Overall, our findings could generate pivotal insights into how re-directing intraneuronal energy channeling may promote neuronal repair in the CNS.

This is a 2021 ARVO Annual Meeting abstract.

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