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

Abstract

The reparative ability of the central nervous system varies widely in the animal kingdom. In the mammalian brain, the regenerative mechanisms are very limited and newly formed neurons do not survive longer, probably due to a non-suitable local environment. On the opposite, fish can repair the brain after injury, with fast and complete recovery of damaged area. The brain of zebrafish, a teleost fish widely used as vertebrate model, also possesses high regenerative properties after injury. Taking advantage of this relevant model, the aim of the present study was to investigate the role of brain-derived neurotrophic factor (BDNF) in the regenerative ability of adult brain, after stab wound telencephalic injury. BDNF is involved in many brain functions and plays key roles in the repair process after traumatic brain lesions. It has been reported that BDNF strengthens the proliferative activity of neuronal precursor cells, facilitates the neuronal migration toward injured areas, and shows survival properties due to its anti-apoptotic effects. BDNF mRNA levels, assessed by quantitative PCR and in situ hybridization at 1, 4, 7, and 15 days after the lesion, were increased in the damaged telencephalon, mostly suddenly after the lesion. Double staining using in situ hybridization and immunocytochemistry revealed that BDNF mRNA was restricted to cells identified as mature neurons. BDNF mRNA expressing neurons mostly increased in the area around the lesion, showing a peak 1 day after the lesion. Taken together, these results highlight the role of BDNF in brain repair processes and reinforce the value of zebrafish for the study of regenerative neurogenesis.

Neuroanatomical distribution and functions of brain‐derived neurotrophic factor in zebrafish (Danio rerio) brain

“…However, if the injured zebrafish is treated with TrkB antagonist ANA‐12, the proliferation fails to increase and remains comparable to the baseline level (Anand & Mondal, ). In case of an experimentally induced injury in the dorsolateral telencephalon of zebrafish brain, BDNF mRNA level increases considerably after 1 day, followed by a progressive decline at 4, 7, and 15 days (Cacialli, D'Angelo, et al, ). Further, as compared to non‐injured control fish, the number of BDNF‐expressing cells increases considerably after the injury, particularly in the lesioned telencephalic hemisphere.…”

“…The double staining ISH/IHC experiments have revealed the expression of BDNF by acetylated tubulin (mature neuronal marker)‐positive cells indicating that BDNF in the adult zebrafish brain is mainly expressed by neurons. Besides this, none of the PCNA‐positive cells express BDNF (Cacialli, D'Angelo, et al, ). Overall, these results indicate that BDNF expressed by mature neurons might be a key player in regulating the adult neurogenesis and reparative brain regeneration process in adult zebrafish.…”

Nerve growth factor is expressed and stored in central neurons of adult zebrafish

“…PCNA, antibody at diluted 1:100, was used to detect proliferative cells (Clone PC10; Dako, Glostrup, Denmark; REF: M0879; RRID: AB_2160651). This antibody is a marker of proliferating cells in vertebrate species, including zebrafish (Pellegrini et al., ; Marz et al., ; Cacialli et al., , ,b). MAP2 antibody, diluted 1:100, was used to detect neurons [sc‐74422 MAP‐2 (A‐8); Santa Cruz Biotechnology, Santa Cruz, CA, USA].…”

“…Among teleost fish, zebrafish ( Danio rerio ) is widely used as model species for developmental genetic studies and functional mechanisms of numerous genes responsible for human diseases (D'Angelo et al., ,b). In addition, zebrafish brain has been largely utilized in numerous studies devoted to adult neurogenesis (Pellegrini et al., ; Diotel et al., ; Coumailleau et al., ; Than‐Trong & Bally‐Cuif, ; Anand & Mondal, ) and regenerative ability after injury (Cosacak et al., ; Alunni & Bally‐Cuif, ; Cacialli et al., ,b).…”

“…The distribution pattern of neurotrophins and their Trk receptors was described in the brain of adult fish (Dalton et al., ,b; D'Angelo et al., , ,b, ,b; Cacialli et al., ; Gatta et al., ). Furthermore, BDNF appeared to be involved in repairing mechanisms of adult zebrafish after traumatic brain injury (Cacialli et al., ,b; Lucini et al., ).…”