Fish-ing for neuroregenerative strategies in senescent teleosts
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1
KU Leuven, Biology, Belgium
Due to the rise in life expectancy, age-associated neurodegenerative diseases show an increasing prevalence. Intensive research efforts are therefore focused on stimulating neuroregeneration in the central nervous system (CNS), a capacity that is unfortunately very limited in adult mammals and remains challenging to induce, especially in an aging environment. As aging seriously impacts on CNS functioning, the search for novel reparative strategies for age-related neurodegenerative diseases should preferably be performed in the aged CNS. This immediately pinpoints the urgent need for a well-characterized senescent animal model in which the impact of aging on regeneration can be adequately studied. In contrast to mammals, teleost fish have a remarkable neurogenic and regenerative potential in their adult CNS, already making them a preferred model organism in a myriad of comparative studies investigating the underlying mechanisms of successful regeneration. Moreover, over the past decade, several teleost species, such as the zebrafish (Danio rerio) and the African turquoise killifish (Nothobranchius furzeri), have been exploited in gerontology research. As their aging shows characteristics similar to humans, these small teleosts are ideally suited to investigate the necessary underlying mechanisms to support successful regeneration in an aging environment.
As such, over the past four years, our team implemented the zebrafish as gerontology model and characterized retinotectal regeneration in young (5 months) and aged (2 years) zebrafish subjected to optic nerve crush (ONC). Using both in vivo and ex vivo axonal regeneration assays, our data demonstrate an overall delay in optic nerve regeneration with aging. Indeed, we observed an age-related decrease and/or misregulation of both the intrinsic RGC growth potential and the extrinsic inflammatory response, suggesting that the observed decline in axonal outgrowth potential of aged zebrafish is most likely the result of general cellular senescence. However, although showing a decelerated regenerative potential, aged zebrafish are still able to complete reinnervation of the optic tectum over time and as such restore vision. We are currently investigating the underlying mechanisms of this striking restorative capacity in old fish.
Unfortunately, the relatively long lifespan of zebrafish puts a certain restriction on investigating neuroregenerative capacity at old age. N. furzeri, as an upcoming aging model, is therefore a perfect replenishment/alternative to speed up age-related regenerative decline research. In fact, by using this small vertebrate in parallel with our well-established zebrafish model, and by examining the differences as well as the similarities of their regenerative as well as aging processes, new information about important key players of successful neuroregeneration can be discovered. Therefore, the ONC model is currently optimized and characterized in depth in killifish, already showing remarkable overlap in time-course of optic nerve regeneration.
In summary, we introduce the fish visual system as a valuable model to shed light on the impact of aging processes on fish optic nerve regeneration, thereby contributing to the elucidation of the cellular and molecular mechanisms underlying successful neuroregeneration and the search for effective neuroregenerative therapies in the aged mammalian CNS.
Keywords:
Nothobranchius furzeri,
danio rerio,
aging model,
Retina,
optic nerve regeneration,
optic nerve crush,
Characterization of intrinsic and extrinsic responses
Conference:
12th National Congress of the Belgian Society for Neuroscience, Gent, Belgium, 22 May - 22 May, 2017.
Presentation Type:
Poster Presentation
Topic:
Disorders of the Nervous System
Citation:
Vanhunsel
S,
Van Houcke
J,
Bollaerts
I,
Beckers
A,
Lemmens
K,
De Groef
L and
Moons
L
(2019). Fish-ing for neuroregenerative strategies in senescent teleosts.
Front. Neurosci.
Conference Abstract:
12th National Congress of the Belgian Society for Neuroscience.
doi: 10.3389/conf.fnins.2017.94.00108
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Received:
20 Apr 2017;
Published Online:
25 Jan 2019.
*
Correspondence:
Ms. Sophie Vanhunsel, KU Leuven, Biology, Leuven, 3000, Belgium, sophie.vanhunsel@kuleuven.be