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Effects of tenuifolin on rest/wake behaviour in zebrafish.

ABSTRACT: Insomnia is a common sleep disorder with a high prevalence and substantial adverse consequences. There is growing interest in identifying novel therapeutics from herbal medicine. Tenuifolin is a major constituent of the well-known anti-insomnia herb Radix Polygala. The present study investigated the neural activity in response to tenuifolin during rest/wake behaviour in zebrafish and identified the potential biological signalling pathways involved. An automatic video tracking system was used to monitor the behavioural response of zebrafish larvae for 24 h after treatment with tenuifolin. In total, six rest/wake parameters were measured and visualized with a behavioural fingerprint. Time series analysis was conducted by averaging the total rest and waking activity in 10 min intervals. A correlation analysis was performed between tenuifolin and well-known compounds to analyse the underlying biological signalling pathways. Reverse transcription-quantitative PCR was also performed to detect the effects of tenuifolin on the transcription of interesting genes associated with the signalling pathways that were potentially involved. The present results suggested tenuifolin significantly increased the total rest time during the dark phase, with a slight effect on the waking activity in zebrafish larvae. This behavioural phenotype induced by tenuifolin is similar to that of selective serotonin reuptake inhibitors and gamma-aminobutyric acid (GABA) agonists. Furthermore, the expression levels of GABA transporter 1 were significantly increased after tenuifolin treatment. No significant difference was determined in other associated genes in untreated control and tenuifolin-treated larvae. The present results suggested that tenuifolin caused sleep-promoting activity in zebrafish and that these effects may be mediated by the serotoninergic systems and the GABAergic systems.

SUBMITTER: Chen ZW

PROVIDER: S-EPMC7027208 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Effects of tenuifolin on rest/wake behaviour in zebrafish.

Chen Zi-Wen ZW Peng Chao-Bao CB Pei Zhong Z Zhang Meng-Ruo MR Yun Tian-Chan TC Yang Zhi-Min ZM Xu Fu-Ping FP

Experimental and therapeutic medicine 20200128 3

Insomnia is a common sleep disorder with a high prevalence and substantial adverse consequences. There is growing interest in identifying novel therapeutics from herbal medicine. Tenuifolin is a major constituent of the well-known anti-insomnia herb Radix Polygala. The present study investigated the neural activity in response to tenuifolin during rest/wake behaviour in zebrafish and identified the potential biological signalling pathways involved. An automatic video tracking system was used to ...[more]

PMID: 32104301

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Project description:UnlabelledDuring embryonic development, regulation of gene expression is key to creating the many subtypes of cells that an organism needs throughout its lifetime. Recent work has shown that maternal genetics and environmental factors have lifelong consequences on diverse processes ranging from immune function to stress responses. The RE1-silencing transcription factor (Rest) is a transcriptional repressor that interacts with chromatin-modifying complexes to repress transcription of neural-specific genes during early development. Here we show that in zebrafish, maternally supplied rest regulates expression of target genes during larval development and has lifelong impacts on behavior. Larvae deprived of maternal rest are hyperactive and show atypical spatial preferences. Adult male fish deprived of maternal rest present with atypical spatial preferences in a novel environment assay. Transcriptome sequencing revealed 158 genes that are repressed by maternal rest in blastula stage embryos. Furthermore, we found that maternal rest is required for target gene repression until at least 6 dpf. Importantly, disruption of the RE1 sites in either snap25a or snap25b resulted in behaviors that recapitulate the hyperactivity phenotype caused by absence of maternal rest Both maternal rest mutants and snap25a RE1 site mutants have altered primary motor neuron architecture that may account for the enhanced locomotor activity. These results demonstrate that maternal rest represses snap25a/b to modulate larval behavior and that early Rest activity has lifelong behavioral impacts.Significance statementMaternal factors deposited in the oocyte have well-established roles during embryonic development. We show that, in zebrafish, maternal rest (RE1-silencing transcription factor) regulates expression of target genes during larval development and has lifelong impacts on behavior. The Rest transcriptional repressor interacts with chromatin-modifying complexes to limit transcription of neural genes. We identify several synaptic genes that are repressed by maternal Rest and demonstrate that snap25a/b are key targets of maternal rest that modulate larval locomotor activity. These results reveal that zygotic rest is unable to compensate for deficits in maternally supplied rest and uncovers novel temporal requirements for Rest activity, which has implications for the broad roles of Rest-mediated repression during neural development and in disease states.

Dataset Information

Effects of tenuifolin on rest/wake behaviour in zebrafish.

Publications

Effects of tenuifolin on rest/wake behaviour in zebrafish.

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