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

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.