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How We Rapidly Respond to Stress: Genetically Modified Zebrafish May Provide an Answer

Contributor Si-Cheng Dai

All of us, at some point in our lives, have encountered stressors—events like public speaking or an approaching deadline that have triggered an imbalance in our body’s internal state. In such moments, our bodies automatically evoke the stress response, changing our physiological state and behaviours to adapt to the threat. For example, our blood pressure may rise, our memory might be enhanced, and we could possibly become more aware of our surroundings. The body’s pituitary gland is a big player in these changes. Its frontal portion contains corticotroph cells, which release adrenocorticotropic hormone (ACTH). This hormone causes the adrenal glands atop the kidneys to secrete the hormone cortisol, which ultimately targets many of our organs to facilitate the stress response.

Corticotroph cells and their associated hormones have a well-known role in slower behavioural adaptations to stress (minutes to hours). Dr. De Marco and his colleagues at the Max Planck Institute for Medical Research in Germany, meanwhile, wanted to establish their role in rapid behavioural adaptations to stress (seconds to minutes).

The team used zebrafish larvae as a model, genetically modifying them to contain bPAC in their corticotroph cells. The enzyme bPAC is activated when exposed to blue light, helping to make ACTH in the cell. Thus, shining blue light (a stressor in its own right) on zebrafish with bPAC was predicted to cause more corticotroph cell activation—and in turn, stronger rapid adaptations—than shining this light on normal zebrafish. To test this, the researchers exposed zebrafish to blue light and immediately assessed their movement, responsiveness to stimuli, and avoidance behaviour.

In both the movement and responsiveness tests, zebrafish with bPAC showed more extreme responses than normal zebrafish. For example, zebrafish with bPAC slowed their movement even more under the light, and swam even faster under the stimulus of higher water temperature. Remarkably, in an avoidance test, zebrafish with bPAC showed a better ability than normal zebrafish to choose different behaviours based on the threat level. Under low power light (a lower-level threat), these fish reduced their swimming movement the most, likely to conserve energy. Meanwhile, under high levels of light (a higher-level threat), these fish performed the most high-energy escape movements, seeming to recognize the increased stakes.

In all three tests, fish with bPAC displayed more rapid behavioural adaptations, supporting a role of the corticotroph cell in the rapid stress response. The fish with bPAC also had the highest cortisol levels when tested, hinting that the release of ACTH followed by that of cortisol might be the way the corticotroph cell causes these rapid changes. There is still a long way to go, but this research gives us a glimpse into how we rapidly respond to stress. Understanding how this phenomenon connects to the rest of the stress response might be a step toward understanding and eventually treating stress-related disorders, from heart disease to depression.

Journal Reference:

1. De Marco RJ, Thiemann T, Groneberg AH, Herget U, Ryu S. Optogenetically Enhanced Pituitary Corticotroph Cell Activity Post-stress Onset Causes Rapid Organizing Effects on Behaviour. Nat Commun. 2016 Sep 20;7:12620

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