ABOVE: A Xenopus laevis tadpole after injection of cyanobacteria into its heart

Unlike plants, animals can’t carry out photosynthesis to generate our own oxygen, yet our brains rely on oxygen to make the massive amounts of energy needed to function. In a study published today (October 13) in iScienceresearchers found a way to harness photosynthesis to supply neurons with oxygen: they injected either cyanobacteria or green algae into Xenopus laevis tadpoles and deprived the animals of oxygen, causing brain activity to cease. Exposing the animals to light, which allowed the microbes to make oxygen from CO2, restored neural activity.

“The authors employ an elegant and easily reproducible experimental approach to examine the effects of activation of photosynthetic organisms as a way to directly increase oxygen levels in the brain,” Diana Martinez, a neuroscientist at Rowan University in New Jersey who was not involved in the study, writes in an email to The Scientist. The work is a proof of principle, she adds, and “an important first step in using natural resources to address pathological impairments” that deplete oxygen in the brain, such as heart attack and stroke.

Neuroscientist Hans Straka of Ludwig Maximilian University of Munich (LMU) and his group are interested in oxygen consumption in the brain and use a well-established technique in which they remove the head of a tadpole and keep it alive and functional for a couple of days in a liquid environment that supplies both oxygen and nutrients. Over lunch, Straka and LMU plant biologist Jörg Nickelsen got to talking about how they might work together on a project. Their solution: investigate whether it would be possible to have photosynthetic microorganisms supply the brain with oxygen.

Nickelsen’s then-postdoc Myra Chávez Rosas, who is now at the University of Bern in Switzerland, grew green algae (Chlamydomonas reinhardtii) and cyanobacteria (Synechocystis sp. PCC6803), which both produce oxygen upon illumination. Graduate student Suzan Özugur, who has since graduated from Straka’s lab, then injected a slurry of either algae or cyanobacteria into the hearts of tadpoles just after their forelimbs emerged. Their hearts pumped the microbes throughout the animals’ vessels, including into the vasculature of the brain.

Can we get away from breathing as a way to keep our brains going?

—Ryan Kerney, Gettysburg College

The team found that upon illumination, oxygen concentration in the ventricles of injected animals went up. Untreated animals or those that received strains of algae or cyanobacteria that were mutated to not produce oxygen did not have an increase in oxygen concentration. When the researchers depleted oxygen from the water the animals swam in, neuronal activity, as measured by electrical recordings of representative nerves, stopped. But they were able to restart activity in the brain by shining light on animals who’d received injections of microorganisms. When they turned off the light, neuronal activity ceased again.

Although the experiment was a success, Martinez notes it’s not clear whether the findings could be translated to treat conditions in which the brain is starved for oxygen. “The first issue is that Xenopus laevis tadpoles are transparent and light can easily pass through the skin to activate photosynthetic machinery to produce oxygen. Use in more complex animals would . . . be difficult, as light does not easily traverse the skin and may not reach the vasculature to activate the photosynthetic organisms,” she writes. Additionally, while low oxygen can be a problem, excess oxygen can also exacerbate brain injuries. “Thus, 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.” Trying the technique in brain organoids and slices first would give more insight into its physiological effects, she adds.

Straka acknowledges that the research is still at the early stages and that taking the strategy to the clinic is “very far away.” In the near term, his team will focus on several questions, including the immunological effects of introducing the photosynthesizing microorganisms, and whether or not the sugars that the microbes produce can be used by the tadpoles’ brains.

“Over the last decade, there are quite a few projects where people have been trying to set up artificial symbiotic associations with algae, in order to augment in some way or manipulate vertebrate physiology, which is really radical,” says Ryan Kerney, a biologist who studies symbioses between algae and salamanders at Gettysburg College in Pennsylvania and did not participate in the new work. Approaches where microbes are artificially inserted into cells or into tissues to modify their function are largely unregulated and under-scrutinized in comparison to widely used genetic modification techniques such as CRISPR that target one gene, Kerney adds. The unknowns, as well as examples of pathogenic algae, make this strategy a bit risky, he notes. “But the potential implications are also just fascinating to speculate about: Can we get away from breathing as a way to keep our brains going?”