TrkB receptor antagonism inhibits stab injury induced proliferative response in adult zebrafish (Danio rerio) brain

Neurosci Lett. 2018 Apr 13:672:28-33. doi: 10.1016/j.neulet.2018.02.040. Epub 2018 Feb 20.

Abstract

The Tropomyosin related kinase B (TrkB) receptor, is known to promote neuronal maturation, differentiation, maintenance and survival through its cognate ligands Brain derived neurotrophic factor (BDNF) and neurotrophin 4 (NT4). BDNF, NT4 and TrkB are highly conserved proteins among vertebrates. Although the role of TrkB during brain development is well established, its role in adult neurogenesis and brain regeneration awaits thorough investigation. In this study, we used the zebrafish stab wound injury model to determine whether the injury induced regeneration response in the telencephalon region is governed by TrkB or not. We induced stab wound injury in the mid-dorsal region of telencephalon of ANA-12 (selective TrkB antagonist) treated and non-treated zebrafish brain and examined the proliferation activity in selected brain regions using immunohistochemistry. We found that proliferation activity was significantly low in ANA-12 injected injured fishes as compared to vehicle control injured fishes. Other major findings of the study include the temporal pattern of proliferation activity after an injury and activation of adult neural stem cells (aNSCs) situated distantly apart from the injury site in the adult zebrafish brain.

Keywords: Adult zebrafish; BDNF; Brain regeneration; Stab injury; TrkB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Azepines / pharmacology*
  • Benzamides / pharmacology*
  • Brain / drug effects*
  • Brain / metabolism
  • Cell Proliferation / drug effects*
  • Proliferating Cell Nuclear Antigen / metabolism
  • Receptor, trkB / antagonists & inhibitors*
  • Receptor, trkB / metabolism
  • Wound Healing / drug effects*
  • Zebrafish

Substances

  • ANA 12 compound
  • Azepines
  • Benzamides
  • Proliferating Cell Nuclear Antigen
  • Receptor, trkB