PUBLICATION
Decreased thyroid hormone signaling accelerates the reinnervation of the optic tectum following optic nerve crush in adult zebrafish
- Authors
- Bhumika, S., Lemmens, K., Vancamp, P., Moons, L., Darras, V.M.
- ID
- ZDB-PUB-150429-12
- Date
- 2015
- Source
- Molecular and cellular neurosciences 68: 92-102 (Journal)
- Registered Authors
- Darras, Veerle
- Keywords
- inflammation, neuroregeneration, optic nerve, thyroid hormone, zebrafish
- MeSH Terms
-
- Gene Expression Regulation/drug effects
- Optic Nerve Injuries/drug therapy
- Optic Nerve Injuries/physiopathology*
- Cell Proliferation/drug effects
- Hormone Antagonists/pharmacology
- Superior Colliculi/drug effects
- Superior Colliculi/physiology*
- Time Factors
- Neurogenesis/drug effects
- Disease Models, Animal
- Signal Transduction/drug effects
- Signal Transduction/physiology*
- Thyroid Hormones/genetics
- Thyroid Hormones/metabolism*
- Thyroid Hormones/therapeutic use
- Heterocyclic Compounds, 1-Ring/therapeutic use
- Zebrafish
- Tyrosine 3-Monooxygenase/genetics
- Tyrosine 3-Monooxygenase/metabolism
- Animals
- Brain/drug effects
- Brain/metabolism
- Brain/pathology
- Retina/metabolism
- Retina/pathology
- Nerve Tissue Proteins/genetics
- Nerve Tissue Proteins/metabolism
- Iopanoic Acid/therapeutic use
- Lysine/analogs & derivatives
- Lysine/metabolism
- Nerve Regeneration/drug effects
- Nerve Regeneration/physiology*
- PubMed
- 25913150 Full text @ Mol. Cell Neurosci.
Citation
Bhumika, S., Lemmens, K., Vancamp, P., Moons, L., Darras, V.M. (2015) Decreased thyroid hormone signaling accelerates the reinnervation of the optic tectum following optic nerve crush in adult zebrafish. Molecular and cellular neurosciences. 68:92-102.
Abstract
The regenerative capacity of the adult mammalian central nervous system (CNS) is poor and finding ways to stimulate long distance axonal regeneration in humans remains a challenge for neuroscientists. Thyroid hormones, well known for their key function in CNS development and maturation, more recently also emerged as molecules influencing regeneration. While several studies investigated their influence on peripheral nerve regeneration, in vivo studies on their role in adult CNS regeneration remain scarce. We therefore investigated the effect of lowering T3 signaling on the regeneration of the optic nerve (ON) following crush in zebrafish, a species where full recovery occurs spontaneously. Adult zebrafish were exposed to iopanoic acid (IOP), which lowered intracellular 3,5,3'-triiodothyronine (T3) availability, or to the thyroid hormone receptor β antagonist methylsulfonylnitrobenzoate (C1). Both treatments accelerated optic tectum (OT) reinnervation. At 7 days post injury (7 dpi) there was a clear increase in the biocytin labeled area in the OT following anterograde tracing as well as an increased immunostaining of Gap43, a protein expressed in outgrowing axons. This effect was attenuated by T3 supplementation to IOP-treated fish. ON crush induced very limited cell death and proliferation at the level of the retina in control, IOP- and C1-treated fish. The treatments also had no effect on the mRNA upregulation of the regeneration markers gap43, tub1a, socs3b at the level of the retina at 4 and 7 dpi. We did, however, find a correlation between the accelerated OT reinnervation and a more rapid resolution of microglia/macrophages in the ON and the OT of IOP-treated fish. Taken together these data indicate that lowering T3 signaling accelerates OT reinnervation following ON crush in zebrafish and that this is accompanied by a more rapid resolution of the inflammatory response.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping