No abstract

The effects of temperature and salinity on the settlement, subsequent survival and development of the copepodids of Lepeophtheirus salmonis on Atlantic salmon were investigated experimentally. There was a significantly greater settlement and survival of copepodids at 10 days post‐infection (dpi) at 12 °C compared with at 7 °C at a constant salinity of 34‰. Development of L. salmonis was also more rapid at 12 °C. Settlement was significantly greater at a salinity of 34‰ than at 24‰. In one experiment, survival at 10 dpi was significantly greater at 34‰; however, a second experiment found that there was no significant difference between the two saline levels. This may have been because of a rise in water temperature for 2 dpi, which appears to have overridden the effect of low salinity. Development of L. salmonis was more rapid at 34‰. Copepodids settled on all of the external surfaces of the salmon, although the proportion on different surfaces varied between experiments. The gills, particularly at low temperatures, the body surface, and the pectoral and dorsal fins were especially favoured.

Drug-induced liver injury (DILI) is a major challenge in clinical medicine and drug development. New models are needed for predicting which potential therapeutic compounds will cause DILI in humans, and new markers and mediators of DILI still need to be identified. This review highlights the strengths and weaknesses of using zebrafish as a high-throughput in vivo model for studying DILI. Although the zebrafish liver architecture is different from that of the mammalian liver, the main physiological processes remain similar. Zebrafish metabolize drugs using similar pathways to those in humans; they possess a wide range of cytochrome P450 enzymes that enable metabolic reactions including hydroxylation, conjugation, oxidation, demethylation and de-ethylation. Following exposure to a range of hepatotoxic drugs, the zebrafish liver develops histological patterns of injury comparable to those of mammalian liver, and biomarkers for liver injury can be quantified in the zebrafish circulation. The zebrafish immune system is similar to that of mammals, but the zebrafish inflammatory response to DILI is not yet defined. In order to quantify DILI in zebrafish, a wide variety of methods can be used, including visual assessment, quantification of serum enzymes and experimental serum biomarkers and scoring of histopathology. With further development, the zebrafish may be a model that complements rodents and may have value for the discovery of new disease pathways and translational biomarkers.

Key points• Glucocorticoids are known to be present in the developing zebrafish embryo but little is known about their physiological role at this early stage.• The zebrafish embryo demonstrates a functional glucocorticoid system from around 48 h post fertilisation.• This system and the stress response is amenable to pharmacological and genetic manipulation in a manner predicted by mammalian physiology.• Glucocorticoids play a key developmental role in hatching, swimming and stress response.• The zebrafish embryo is a relevant model for the study of glucocorticoid physiology.Abstract While glucocorticoids (GCs) are known to be present in the zebrafish embryo, little is known about their physiological roles at this stage. We hypothesised that GCs play key roles in stress response, hatching and swim activity during early development. To test this, whole embryo cortisol (WEC) and corticosteroid-related genes were measured in embryos from 6 to 120 h post fertilisation (hpf) by enzyme linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR). Stress response was assessed by change in WEC following stirring, hypoxia or brief electrical impulses applied to the bathing water. The impact of pharmacological and molecular GC manipulation on the stress response, spontaneous hatching and swim activity at different stages of development was also assessed. WEC levels demonstrated a biphasic pattern during development with a decrease from 0 to 36 hpf followed by a progressive increase towards 120 hpf. This was accompanied by a significant and sustained increase in the expression of genes encoding cyp11b1 (GC biosynthesis), hsd11b2 (GC metabolism) and gr (GC receptor) from 48 to 120 hpf. Metyrapone (Met), an inhibitor of 11β-hydroxylase (encoded by cyp11b1), and cyp11b1 morpholino (Mo) knockdown significantly reduced basal and stress-induced WEC levels at 72 and 120 hpf but not at 24 hpf. Spontaneous hatching and swim activity were significantly affected by manipulation of GC action from approximately 48 hpf onwards. We have identified a number of key roles of GCs in zebrafish embryos contributing to adaptive physiological responses under adverse conditions. The ability to alter GC action in the zebrafish embryo also highlights its potential value for GC research.