Severe hypoxia exposure inhibits larval brain development but does not affect the capacity to mount a cortisol stress response in zebrafish

Abstract

Fish nursery habitats are increasingly hypoxic and the brain is recognized as highly hypoxia-sensitive, yet there is a lack of information on the effects of hypoxia on the development and function of the larval fish brain. Here, we tested the hypothesis that by inhibiting brain development, larval exposure to severe hypoxia has persistent functional effects on the cortisol stress response in zebrafish (Danio rerio). Exposing 5 days post-fertilization (dpf) larvae to 10% dissolved O2 (DO) for 16 h only marginally reduced survival, but it decreased forebrain neural proliferation by 55%, and reduced the expression of neurod1, gfap, and mbpa, markers of determined neurons, glia, and oligodendrocytes, respectively. The 5 dpf hypoxic exposure also elicited transient increases in whole body cortisol and in crf, uts1, and hsd20b2 expression, key regulators of the endocrine stress response. Hypoxia exposure at 5 dpf also inhibited the cortisol stress response to hypoxia in 10 dpf larvae and increased hypoxia tolerance. However, 10% DO exposure at 5 dpf for 16h did not affect the cortisol stress response to a novel stressor in 10 dpf larvae or the cortisol stress response to hypoxia in adult fish. Therefore, while larval exposure to severe hypoxia can inhibit brain development, it also increases hypoxia tolerance. These effects may transiently reduce the impact of hypoxia on the cortisol stress response but not its functional capacity to respond to novel stressors. We conclude that the larval cortisol stress response in zebrafish has a high capacity to cope with severe hypoxia-induced neurogenic impairment.

Intergenerational plasticity to cycling high temperature and hypoxia affects offspring stress responsiveness and tolerance in zebrafish

“…As predicted, we observed that offspring derived from parents exposed to diel cycles of heat stress and hypoxia have a reduced endocrine stress response when faced with the same challenge as larval fish. Consistent with the observation that either acute heat stress (36°C for 10 min; Yeh et al, 2013 ) or hypoxia exposure (10% DO for 2 h; Mikloska et al, 2022 ) stimulates the HPI axis in 5 dpf larval zebrafish, we demonstrate that the two stressors combined (36°C and 20% DO for 20 min) elicit an increase in whole body cortisol in control larvae, but has no effect in the larvae derived from parents exposed to cycles of thermal stress and hypoxia. In contrast, the 5 dpf larvae from both parental treatments had a similar increase in whole body cortisol following a swirling stressor, and the magnitude of the response was consistent with a previous observation ( Williams et al, 2017 ).…”

“…Together, these results suggest that sustained parental exposure to cycles of thermal stress and hypoxia increase the tolerance of larvae to a similar challenge but does not affect their capacity to mount a cortisol stress response to a novel stressor. Although previous studies using 5 dpf zebrafish larvae have shown that stressors can upregulate hsd11b2 and hsd20b2 expression ( Tokarz et al, 2013 ; Mikloska et al, 2022 ), here we provide novel evidence that acute exposure to combined heat stress and hypoxia also stimulates the expression of both transcripts. Given that hsd11b2 and hsd20b2 expression is cortisol-dependent ( Tokarz et al, 2013 ) and that larvae derived from parents exposed to cycles of thermal stress and hypoxia did not mount a cortisol stress response when challenged with a similar stressor, the finding that larvae from both parental treatments upregulated these transcripts was unexpected.…”

“…development, growth, reproduction and survival) and their overall biomass ( Díaz and Rosenberg, 2011 ; Jenny et al, 2016 ; Sampaio et al, 2021 ; Harvey et al, 2022 ). Beyond extreme events, climate-change-driven increases in temperature are increasing the prevalence, severity and variability of environmental hypoxia, conditions that are negatively impacting offspring development and recruitment ( Smith and Able, 2003 ; Cheek et al, 2009 ; Stierhoff et al, 2009 ; Baumann et al, 2015 ; Campbell and Rice, 2014 ; Tommasi et al, 2015 ; Rooper et al, 2019 ; Mikloska et al, 2022 ). Therefore, there is an urgent need to understand the capacity of fishes to adjust their phenotype and buffer against the combined stressor of high temperature and hypoxia.…”

Asiatic acid in Centella asiatica extract towards morphological development in an intermittent hypoxia intrauterine embryo model and molecular prediction pathway of insulin-like growth factor-1 (IGF-1) receptor signalling

“…Adult zebrafish of both sexes were kept in a 60-l glass aquarium with a female and male ratio of 2:1. Adult fish were maintained at a density of 4–5 fish l -1 ( Mikloska et al , 2022 ). The temperature was set at 28°C ± 1°C, and the light/dark cycle was 14:10 hours.…”

“…Egg water was replaced twice a day. Neither eggs nor embryos were reared for 12 hours:12 hours in light: dark radiation ( Mikloska et al , 2022 ).…”