Ustilaginoidin D induces hepatotoxicity and behaviour aberrations in zebrafish larvae

Abstract Background Early-onset familial Alzheimer’s disease (EOfAD) is promoted by dominant mutations, enabling the study of Alzheimer’s disease (AD) pathogenic mechanisms through generation of EOfAD-like mutations in animal models. In a previous study, we generated an EOfAD-like mutation, psen1Q96_K97del, in zebrafish and performed transcriptome analysis comparing entire brains from 6-month-old wild type and heterozygous mutant fish. We identified predicted effects on mitochondrial function and endolysosomal acidification. Here we aimed to determine whether similar effects occur in 7 day post fertilization (dpf) zebrafish larvae that might be exploited in screening of chemical libraries to find ameliorative drugs. Results We generated clutches of wild type and heterozygous psen1Q96_K97del 7 dpf larvae using a paired-mating strategy to reduce extraneous genetic variation before performing a comparative transcriptome analysis. We identified 228 differentially expressed genes and performed various bioinformatics analyses to predict cellular functions. Conclusions Our analyses predicted a significant effect on oxidative phosphorylation, consistent with our earlier observations of predicted effects on ATP synthesis in adult heterozygous psen1Q96_K97del brains. The dysregulation of minichromosome maintenance protein complex (MCM) genes strongly contributed to predicted effects on DNA replication and the cell cycle and may explain earlier observations of genome instability due to PSEN1 mutation. The upregulation of crystallin gene expression may be a response to defective activity of mutant Psen1 protein in endolysosomal acidification. Genes related to extracellular matrix (ECM) were downregulated, consistent with previous studies of EOfAD mutant iPSC neurons and postmortem late onset AD brains. Also, changes in expression of genes controlling iron ion transport were observed without identifiable changes in the prevalence of transcripts containing iron responsive elements (IREs) in their 3′ untranslated regions (UTRs). These changes may, therefore, predispose to the apparent iron dyshomeostasis previously observed in 6-month-old heterozygous psen1Q96_K97del EOfAD-like mutant brains.

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Tryptophan-tagged peptide from serine threonine-protein kinase of Channa striatus improves antioxidant defence in L6 myotubes and attenuates caspase 3–dependent apoptotic response in zebrafish larvae

Fish Physiology and Biochemistry ◽

10.1007/s10695-020-00912-7 ◽

2021 ◽

Author(s):

Praveen Kumar Issac ◽

Christy Lite ◽

Ajay Guru ◽

Manikandan Velayutham ◽

Giva Kuppusamy ◽

...

Keyword(s):

Protein Kinase ◽

Caspase 3 ◽

Apoptotic Response ◽

Antioxidant Defence ◽

Channa Striatus ◽

Zebrafish Larvae ◽

L6 Myotubes

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Automatic and Robust Estimation of Heart Rate in Zebrafish Larvae

IEEE Transactions on Automation Science and Engineering ◽

10.1109/tase.2017.2705240 ◽

2018 ◽

Vol 15 (3) ◽

pp. 1041-1052 ◽

Cited By ~ 2

Author(s):

Syam Krishna ◽

Kiranam Chatti ◽

Ramesh R. Galigekere

Keyword(s):

Heart Rate ◽

Robust Estimation ◽

Zebrafish Larvae

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Concentration-dependent transcriptome of zebrafish larvae for environmental bisphenol S assessment

Ecotoxicology and Environmental Safety ◽

10.1016/j.ecoenv.2021.112574 ◽

2021 ◽

Vol 223 ◽

pp. 112574

Author(s):

Feng Yang ◽

Ziyu Zhao ◽

Haiji Zhang ◽

Liping Zhou ◽

Liang Tao ◽

...

Keyword(s):

Bisphenol S ◽

Zebrafish Larvae

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Standardized Method for the Assessment of Behavioral Responses of Zebrafish Larvae

Biomedicines ◽

10.3390/biomedicines9080884 ◽

2021 ◽

Vol 9 (8) ◽

pp. 884

Author(s):

Hideyuki Maeda ◽

Noritoshi Fukushima ◽

Akihiro Hasumi

Keyword(s):

Early Stage ◽

Scientific Evidence ◽

Video Tracking ◽

Abnormal Behavior ◽

Laboratory Setting ◽

Zebrafish Larvae ◽

Experimental Systems ◽

Standardized Method ◽

Life Phenomena ◽

And Behavior

Zebrafish are easy to breed in a laboratory setting as they are extremely fertile and produce dozens of eggs per set. Because zebrafish eggs and the skin of the early-stage larvae are transparent, their embryos and the hearts and muscles of their larvae can be easily observed. Multiple rapid analyses of heart rate and behavior can be performed on these larvae simultaneously, enabling investigation of the influence of neuroactive substances on abnormal behavior, death, and associated pathogenetic mechanisms. Zebrafish larvae are becoming increasingly popular among researchers and are used in laboratories worldwide to study various vertebrate life phenomena; more experimental systems using zebrafish will undoubtedly be developed in the future. However, based on the available literature, we believe that the conceptualization of a protocol based on scientific evidence is necessary to achieve standardization. We exposed zebrafish larvae at 6–7 days post-fertilization to 50 repeated light–dark stimuli at either 15-min or 5-min intervals. We measured the traveled distance and habituation time through a video tracking apparatus. The traveled distance stabilized after the 16th repetition when the zebrafish were exposed to light–dark stimuli at 15-min intervals and after the 5th repetition when exposed at 5-min intervals. Additionally, at 15-min intervals, the peak of the traveled distance was reached within the first minute in a dark environment, whereas at 5-min intervals, it did not reach the peak even after 5 min. The traveled distance was more stable at 5-min intervals of light/dark stimuli than at 15-min intervals. Therefore, if one acclimatizes zebrafish larvae for 1 h and collects data from the 5th repetition of light/dark stimuli at intervals of 5 min in the light/dark test, a stable traveled distance result can be obtained. The establishment of this standardized method would be beneficial for investigating substances of unknown lethal concentration.

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Fisetin inhibits lipopolysaccharide-induced inflammatory response by activating β-catenin, leading to a decrease in endotoxic shock

Scientific Reports ◽

10.1038/s41598-021-87257-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ilandarage Menu Neelaka Molagoda ◽

Jayasingha Arachchige Chathuranga C Jayasingha ◽

Yung Hyun Choi ◽

Rajapaksha Gedara Prasad Tharanga Jayasooriya ◽

Chang-Hee Kang ◽

...

Keyword(s):

Glycogen Synthase ◽

Endotoxic Shock ◽

Inflammatory Activity ◽

Prostaglandin E ◽

Necrosis Factor Alpha ◽

Zebrafish Larvae ◽

Proinflammatory Mediators ◽

Tnf Α ◽

Anti Inflammatory ◽

Gsk 3Β

AbstractFisetin is a naturally occurring flavonoid that possesses several pharmacological benefits including anti-inflammatory activity. However, its precise anti-inflammatory mechanism is not clear. In the present study, we found that fisetin significantly inhibited the expression of proinflammatory mediators, such as nitric oxide (NO) and prostaglandin E2 (PGE2), and cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Additionally, fisetin attenuated LPS-induced mortality and abnormalities in zebrafish larvae and normalized the heart rate. Fisetin decreased the recruitment of macrophages and neutrophils to the LPS-microinjected inflammatory site in zebrafish larvae, concomitant with a significant downregulation of proinflammatory genes, such as inducible NO synthase (iNOS), cyclooxygenase-2a (COX-2a), IL-6, and TNF-α. Fisetin inhibited the nuclear localization of nuclear factor-kappa B (NF-κB), which reduced the expression of pro-inflammatory genes. Further, fisetin inactivated glycogen synthase kinase 3β (GSK-3β) via phosphorylation at Ser9, and inhibited the degradation of β-catenin, which consequently promoted the localization of β-catenin into the nucleus. The pharmacological inhibition of β-catenin with FH535 reversed the fisetin-induced anti-inflammatory activity and restored NF-κB activity, which indicated that fisetin-mediated activation of β-catenin results in the inhibition of LPS-induced NF-κB activity. In LPS-microinjected zebrafish larvae, FH535 promoted the migration of macrophages to the yolk sac and decreased resident neutrophil counts in the posterior blood island and induced high expression of iNOS and COX-2a, which was accompanied by the inhibition of fisetin-induced anti-inflammatory activity. Altogether, the current study confirmed that the dietary flavonoid, fisetin, inhibited LPS-induced inflammation and endotoxic shock through crosstalk between GSK-3β/β-catenin and the NF-κB signaling pathways.

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