Low Oxygen Impairs Brain Development in Fish, but the Fish Aren’t Stressed About It

By Megan Fluit

20 June 2022


An adult zebrafish with algae in the background.

An adult zebrafish (Danio rerio) (Colourbox.com) 


If you have ever climbed a mountain, you may have experienced altitude sickness, a condition that occurs in humans due to low oxygen levels at high altitudes. Oxygen is critical to survival for most organisms, and the brain is especially reliant on an adequate supply of oxygen. When an organism does not have sufficient oxygen to support normal function, this is termed hypoxia.

While this phenomenon may be rare for land-dwelling creatures, it is much more common in aquatic environments.

“There are a number of different reasons why hypoxia is common in aquatic environments,” says Dr. Nicholas Bernier, who leads the Stress Neuroendocrinology Lab in the Department of Integrative Biology.

“It's getting worse now because of oxygen depletion induced by excess nutrients and phytoplankton in waterways, but also because of climate change. Warmer waters contain less oxygen, so as you get more extreme warm events, you get waters that are more hypoxic.”

Bernier, along with master’s student Kristina Mikloska and undergraduate researcher Zoe Zrini, recently published a study showing that hypoxia can dramatically impair brain development in zebrafish larvae.

They began the experiment by determining the survival of zebrafish larva at different concentrations of dissolved oxygen to identify the level of hypoxia just above the limit of survival (10% dissolved oxygen). They then used this concentration to examine the effect of low oxygen on brain development and found that it reduced brain cell proliferation by 55%.

The findings led the team to wonder if hypoxia might also affect the ability of the fish’s brain to respond to stress later in life.

An animal’s stress response is critical to its survival, because “it mobilizes energy reserves and provides the fuels that are necessary to cope with stressors and can trigger the physiological responses that will enable the animal to survive in the long term,” explains Bernier.

But to the researchers’ surprise, the reduction in brain development in larvae had no long-term impacts on the fish’s ability to generate a stress response. Larvae exposed to hypoxia showed no differences in their stress response when they were re-exposed to hypoxia as adults, or when exposed to an entirely different type of stressor (e.g., the physical stress caused by an eddy or vortex).

Only larva that were re-exposed to hypoxia just five days after their first exposure showed an impaired stress response, and their survival was improved temporarily. Bernier calls this “reversible hypoxic preconditioning” because the larvae improved their tolerance to hypoxic environments in the short-term, but the adaptation reverses before they reach adulthood.

The results leave the research team with several interesting questions to pursue. For example, how is hypoxia different than other types of stressors in terms of how the stress response is regulated? And what happens if an animal is exposed to hypoxia chronically? For the latter question, initial research in the Bernier lab suggests that chronic hypoxia greatly suppresses the stress response.

It is also possible that hypoxia-induced impairments in neural development could contribute to other maladaptive changes in zebrafish like cognitive deficits or aggressive behaviour.

Says Bernier, “If estuaries are becoming more and more hypoxic worldwide, the long-term physiological consequences can have all kinds of repercussions for fisheries and for fish populations in general. This is why it is critical to understand the full physiological impact.”


Funding was provided by the Natural Sciences and Engineering Research Council of Canada.


Read the full study in the Journal of Experimental Biology.

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