Expression and Localization of BDNF/TrkB System in the Zebrafish Inner Ear

Abstract

Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, is involved in multiple and fundamental functions of the central and peripheral nervous systems including sensory organs. Despite recent advances in knowledge on the functional significance of BDNF and TrkB in the regulation of the acoustic system of mammals, the localization of BDNF/TrkB system in the inner ear of zebrafish during development, is not well known. Therefore, the goal of the present study is to analyze the age-dependent changes using RT-PCR, Western Blot and single and double immunofluorescence of the BDNF and its specific receptor in the zebrafish inner ear. The results showed the mRNA expression and the cell localization of BDNF and TrkB in the hair cells of the crista ampullaris and in the neuroepithelium of the utricle, saccule and macula lagena, analyzed at different ages. Our results demonstrate that the BDNF/TrkB system is present in the sensory cells of the inner ear, during whole life. Therefore, this system might play a key role in the development and maintenance of the hair cells in adults, suggesting that the zebrafish inner ear represents an interesting model to study the involvement of the neurotrophins in the biology of sensory cells

Localization of Neurotrophin Specific Trk Receptors in Mechanosensory Systems of Killifish (Nothobranchius guentheri)

“…Therefore, the loss of sensory cells in humans leads to a wide range of inner ear disorders with a permanent reduction of hearing and balance. In this way, our results demonstrate, for the first time, that also the sensory cells of the inner ear and lateral line system of N. guentheri , as previously observed in zebrafish [ 15 , 68 , 69 ], are very similar, from a morpho-physiological point of view, to human sensory cells. Moreover, fishes maintain the possibility to regenerate the hair cells following damage caused by a traumatic event, intense acoustic stimuli, environmental insults, and pharmacological or ototoxic chemicals treatment.…”

“…The obtained results of this report are in agreement with previous studies performed in different species of fish, including zebrafish ( Danio rerio ), sea bass ( Dicentrarchus labrax ), salmon ( Salmo salar ), and trout ( Salmo trutta ) regarding the localization of Trk receptors in the hair cells of mechanoreceptor tissue of fish auditory systems [ 11 , 12 , 13 , 14 , 16 ]. In recent papers from our group of investigation, the expression and localization of BDNF/TrkB system in the lateral line and inner ear of zebrafish were showed [ 15 ]. In contrast, in this study, no immunoreaction for BDNF and TrkB was observed in the hair cells of N. guentheri .…”

“…As in other vertebrates, neurotrophins and their specific receptors have been localized in the fish nervous system, including sensory organs. Particularly, the occurrence of neurotrophins was also demonstrated in fish inner ear and LLS [ 3 , 11 , 12 , 13 , 14 , 15 , 16 ]. Moreover, NTs and Trk receptors were also found in the zebrafish brain [ 17 , 18 , 19 , 20 , 21 ], retina [ 14 , 22 ], taste buds [ 23 ], and in the crypt neurons of the olfactory epithelium [ 24 ].…”

The BDNF/TrkB Neurotrophin System in the Sensory Organs of Zebrafish

“…Moreover, using confocal laser microscopy, the localization of these proteins was demonstrated in the hair cells of the zebrafish inner ear during its whole life ( Figure 2 ). Particularly, the immunolocalization for BDNF and TrkB was observed in the sensory patches of the macule of the utriculus, lagena, and sacculus as well as in the crista ampullaris of the semicircular canals [ 88 ].…”

Molecular Mechanisms of Sensorineural Hearing Loss and Development of Inner Ear Therapeutics

“…An interesting contribution by Germana and colleagues [ 10 ] focused on the development of zebrafish inner ear. The zebrafish is recognized as an important experimental animal model for studying developmental biology and genetics, as well as modelling human disorders including SNHL.…”