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Tadpols 'Revived' by Photosynthetic Microorganisms in Bloodstream

Biologists at the Ludwig-Maximilians-University Munich have developed a method that allows tadpoles of African clawed frogs (Xenopus laevis) to ‘breathe’ by introducing green algae or cyanobacteria into their bloodstream to supply oxygen. The team’s method provides enough oxygen to effectively rescue neurons in the brains of oxygen-deprived tadpoles.


Transcardial injection of green algae/cyanobacteria in Xenopus laevis tadpoles
Transcardial injection of green algae or cyanobacteria in Xenopus laevis tadpoles distributed these photosynthetic microorganisms throughout the CNS causing a light exposure-timed increase of the oxygen concentration upon illumination of the brain; during a general, brain-wide extinction of neuronal activity by sub-atmospheric oxygen levels, green algae, and cyanobacteria were able to reversibly and repetitively reinitiate the spike activity upon illumination, thereby demonstrating the capacity of these microorganisms to rescue brain activity by photosynthetic oxygen. Image credit : Özugur et al., doi: 10.1016/j.isci.2021.103158.

“The algae actually produced so much oxygen that they could bring the nerve cells back to life, if you will,” said Dr. Hans Straka, a researcher in the Department Biology at the Ludwig-Maximilians-University Munich.


“For many people, it sounds like science fiction, but after all, it’s just the right combination of biological schemes and biological principles.”


In nature, algae live harmoniously in sponges, corals, and anemones, providing them with oxygen and even nutrients.


Why not in vertebrates like frogs? To explore the possibility, the team injected green algae (Chlamydomonas reinhardtii) or cyanobacteria (Synechocystis sp.) into tadpole hearts of African clawed frogs.


Transcardial injection of C. reinhardtii, related to Figures 1D–1F


Suspension of microorganisms at a concentration of 1010 cells/ml were injected by repetitive single pressure pulses of 200 ms and 2 bar. Note the ejection of the cyanobacteria into the bilateral aortic vessels with each pulse.


With each heartbeat, the algae inched through blood vessels and eventually reached the brain, turning the translucent tadpole bright green.


Shining light on these tadpoles prompted both microorganisms to pump out oxygen to nearby cells.


After distributing algae to the brain, the researchers isolated the tadpole’s head and placed it in an oxygen bubble bath with essential nutrients that would preserve the functioning of the cells, allowing them to monitor neural activity and oxygen levels.


Transcardial injection and accumulation of photosynthetic microorganisms in blood vessels of Xenopus laevis tadpoles
Transcardial injection and accumulation of photosynthetic microorganisms in blood vessels of Xenopus laevis tadpoles. Image credit : https://doi.org/10.1016/j.isci.2021.103158

As the scientists depleted oxygen from the bath, the nerves ceased firing and fell silent.

However, illuminating the tadpole head restarted the neural activity within 15 to 20 min, which is about two times faster than replenishing the bath with oxygen without the algae.


The revived nerves also performed as well or even better than before oxygen depletion, showing that the team’s method was quick and efficient.


“We succeeded in showing the proof of principle experiment with this method. It was amazingly reliable and robust, and in my eyes, a beautiful approach,” Dr. Straka said.


“Working in principle doesn’t really mean that you could apply it at the end, but it’s the first step in order to initiate other studies.”


While the authors think their findings may someday lead to new therapies for conditions induced by stroke or oxygen-scarce environments, such as underwater and high altitudes, algae are far from ready to enter our blood circulation.


The vertebrate brain cannot be without oxygen for very long before irreversible damage begins to occur. When resting, the brain of the average vertebrate consumes between 2 and 8 percent of the body's available oxygen.


The human brain is the only real exception, guzzling 20 percent of the body's oxygen, despite taking up only 2 percent of our bodies.


The result is that if we don't breathe for five minutes or more, we can suffocate the neurons in our noggins for good – which means that it's not possible to conduct these kinds of experiments in humans.


Organoids or small slices of the human brain could be tested in the lab first. But even if that works, and despite the successful findings among frogs, this crazy idea might simply never work for our own species.


After all, tadpoles are transparent, which means sunlight can easily pass through their skin into their brain, allowing algae or bacteria to photosynthesize and produce robust and constant amounts of oxygen. The element is then carried around the frog's body via the cardiovascular system.


But the human skull isn't see-through, which means we would need to find another theoretical means of triggering photosynthetic organisms in our brain to produce the right amount of oxygen.


For instance, the authors suggest injecting the microorganisms into the cardiovascular system instead. If the microorganisms are in circulation, flowing in your veins and arteries underneath the skin, they will theoretically receive more sunlight.


The team admits this concept is "highly innovative" and "potentially detrimental". If the microorganisms grow out of control they could very well clog our blood vessels.


Plus, as neuroscientist Diana Martinez warned The Scientist, if too much oxygen is produced it can be just as dangerous as oxygen deprivation.


"Thus," Martinez, who was not involved in the study, explained, "the inability of oxygen levels to be controlled properly through the use of these photosynthetic organisms would therefore be just as detrimental as the hypoxia itself."


In other words, simply because it's possible in frogs, doesn't mean it's worth the risk in humans.


Researchers' next step is to see whether the injected algae can survive inside living tadpoles and continue oxygen production without causing an immune response that wreaks havoc on the animals.


“You have to have new ideas and new concepts to explore; this is one of the ways science is driven,” Dr. Straka said.


“If you are open-minded and think it through, all of a sudden, you can see all the possibilities from one idea.”


The results were published online in the journal iScience.





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