Neuronal expression of brain derived neurotrophic factor in the injured telencephalon of adult zebrafish

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It is largely known that reparative mechanisms in mammalian brain are very limited, and newly formed neurons do not survive for long time, probably due to a non‐suitable local environment. The injury to the brain generates damage to neurons, glia, and vascular structures. Secondary damages may be due to glial proliferation leading to scar, which may function as mechanical and biochemical barriers preventing growth of new cells, and lead to axons necrosis and inflammation (for a review see Kyritsis, Kizil, & Brand, 2014). On the opposite, the brain of adult fish have a high regenerative properties after brain injury, with fast and complete recovery of damaged area, without glial scar formation, and several studies indicated that inflammatory signals can have positive influence on the regenerative response in the brain of zebrafish (for a review see Kyritsis et al., 2014). The striking differences in regenerative properties between mammalian and fish brain have been long ascribed to remarkable different adult neurogenesis processes (for a review see Alunni & Bally‐Cuif, 2016). In mammalian brain only two neurogenic regions are well described: the subventricular zone of the lateral ventricle and the subgranular zone of the dentate gyrus in the hippocampus. In fish, neurogenesis continues along the entire adult life in numerous stem cell niches identified in various/many brain sub‐divisions and mostly lining the ventricles, from which newly differentiated neurons start to migrate. Thus, studies on brain regenerative mechanisms in fish have been the subject of numerous researches, due to their potential for the development of new therapeutic approaches (Skaggs, Goldman, & Parent, 2014; Diotel et al., 2013; Zupanc & Sirbulescu, 2011).
Brain‐derived neurotrophic factor (BDNF) is a member of neurotrophin (NT) family. NTs comprise, in addition to BDNF, the nerve growth factor (NGF), NT‐3, NT‐4/5, NT 6/7. The binding to three distinct tyrosine kinase receptors (Trk) A, B and C mediates their activities concerning neuronal proliferation, survival, differentiation and plasticity in many neuronal populations of central and peripheral nervous system (Reichardt, 2006). However, all NTs also bind with low affinity to the common p75 receptor.
In the brain, BDNF plays multiple and important roles. An indirect evidence is given by a common single‐nucleotide polymorphism in the human BDNF gene, resulting in a valine to methionine substitution in the prodomain (Val66Met), which has been shown to lead to memory impairment and susceptibility to neuropsychiatric disorders (Bath & Lee, 2006). In schizophrenia, patients showed in brain tissue reduced BDNF mRNA serum levels (Wysokinski, 2016). In depressed patients BDNF levels appeared lower, and treatment with antidepressants increased serum BDNF levels compared to controls (for a review see Molendijk et al., 2014). During human normal ageing, BDNF plasma levels significantly decreased. In animal models, BDNF content was unchanged or increased in the hippocampus of aged Sprague Dawley or Wistar rats, although its receptors levels were decreased, thus certainly resulting in a weaker BDNF action (Silhol, Bonnichon, Rage, & Tapia‐Arancibia, 2005).
BDNF has also beneficial effects. In Alzheimer disease, in vitro and in vivo studies in rats indicated that BDNF has neuronal protective effects against neurotoxicity caused by amyloid β‐peptide accumulation. In fact BDNF could act as an antioxidative factor since it is known that it increases the level of activity of some antioxidant enzymes (for a review see Tapia‐Arancibia, Aliaga, Silhol, & Arancibia, 2008). Finally, in the treatment of multiple sclerosis, BDNF plays a role in mechanism of re‐myelination (KhorshidAhmad et al., 2016).
In experimental traumatic brain injury (TBI) performed in rodents, BDNF protein expression is modified (Yang et al., 1996; Hicks, Numan, Dhillon, Prasad, & Seroogy, 1997; Hicks et al., 1999; Griesbach, Hovda, Molteni, & Gomez‐Pinilla, 2002; Rostami et al.
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