Brain-derived neurotrophic factor (BDNF) plays a pivotal role in neuronal growth and differentiation, neuronal plasticity, learning, and memory. Using CRISPR/Cas9 technology, we generated a vital Bdnf null mutant line in zebrafish and carried out its molecular and behavioral characterization. Although no defects are evident on a morphological inspection, 66% of coding genes and 37% of microRNAs turned out to be differentially expressed in bdnf−/− compared with wild type sibling embryos. We deeply investigated the circadian clock pathway and confirmed changes in the rhythmic expression of clock (arntl1a, clock1a and clock2) and clock-controlled (aanat2) genes. The modulatory role of Bdnf on the zebrafish circadian clock was then validated by behavioral tests highlighting the absence of circadian activity rhythms in bdnf−/− larvae. The circadian behavior was partially rescued by pharmacological treatment. The bdnf−/− zebrafish line presented here is the first valuable and stable vertebrate model for the study of BDNF-related neurodevelopmental diseases

Loss of circadian rhythmicity in bdnf knockout zebrafish larvae

Frigato, Elena;Bertolucci, Cristiano
Penultimo
;
2022

Abstract

Brain-derived neurotrophic factor (BDNF) plays a pivotal role in neuronal growth and differentiation, neuronal plasticity, learning, and memory. Using CRISPR/Cas9 technology, we generated a vital Bdnf null mutant line in zebrafish and carried out its molecular and behavioral characterization. Although no defects are evident on a morphological inspection, 66% of coding genes and 37% of microRNAs turned out to be differentially expressed in bdnf−/− compared with wild type sibling embryos. We deeply investigated the circadian clock pathway and confirmed changes in the rhythmic expression of clock (arntl1a, clock1a and clock2) and clock-controlled (aanat2) genes. The modulatory role of Bdnf on the zebrafish circadian clock was then validated by behavioral tests highlighting the absence of circadian activity rhythms in bdnf−/− larvae. The circadian behavior was partially rescued by pharmacological treatment. The bdnf−/− zebrafish line presented here is the first valuable and stable vertebrate model for the study of BDNF-related neurodevelopmental diseases
2022
D'Agostino, Ylenia; Frigato, Elena; Noviello, Teresa M R; Toni, Mattia; Frabetti, Flavia; Cigliano, Luisa; Ceccarelli, Michele; Sordino, Paolo; Cerulo, Luigi; Bertolucci, Cristiano; D'Aniello, Salvatore
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/2482360
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