Microalgae capable of stimulating brain activity in case of oxygen deficiency

In vertebrates, oxygen is essential for metabolic processes, as well as for the growth of cells and tissues. In particular, nerve cells in the brain, which have to process large amounts of signals every second, require a large and constant supply of O2. Therefore, hypoxic conditions, caused by the environment or caused, for example, by a stroke, can irreversibly impair brain function. Researchers show that it is possible to increase O2 levels in tissues in a controlled way by injecting phototrophic microorganisms directly into the brain.

Most of the energy needed by the brain is generated by aerobic metabolism, so it depends on a large and constant supply of oxygen. Animals and humans obtain their oxygen from the environment through respiration. However, this can be compromised by pathological causes (in the case of respiratory or heart disease), or in certain specific conditions (diving, flying at high altitude) that reduce the oxygen supply.

In humans, the treatment of hypoxia is generally based on increased O2 administration, which will promote functional recovery and tissue regeneration. This can be done using several methods: oxygen mask, endotracheal intubation tube, or hyperbaric chamber. Photosynthetic organisms, like plants, can produce oxygen on their own, using sunlight as an energy source. A team from the Louis-et-Maximilien University in Munich set out to exploit this ability for the benefit of vertebrates.

Brain activity revived by photosynthesis

Thus, the researchers introduced photosynthetic microorganisms (unicellular green algae and cyanobacteria) directly into the hearts of frog tadpoles of the species Xenopus laevis. In fact, previous studies had already revealed symbiotic interactions between these microorganisms and certain animals, such as sponges, corals or salamanders. Microalgae have also been used in the laboratory as effective sources of O2 to replace the lack of blood perfusion of isolated tissues.

The team used strains of the prokaryotic cyanobacterium Synechocystis sp. PCC6803 and the eukaryotic microalgae C. reinhardtii, which are the most widely used prokaryotic and eukaryotic unicellular model organisms in photosynthesis research, respectively. The progressive vascular dispersion of these microorganisms was made visible by the green coloration of the blood vessels. The lighting used had an intensity of 5400 lux.

When exposed to light, the tadpoles’ brain ventricles produce substantial amounts of oxygen until the light is turned off. “In a severely artificially generated hypoxic environment, which completely abolished neural activity, light-induced O2 production by microorganisms caused a restart of peak neuronal discharge and thus spared brain activity,” write the researchers.

Exposure to light caused an asymptotic increase in O2 concentration in the brain, which remained at a high level until the light was turned off, causing a gradual return to reduced O2 levels (green trace, graph B1). © S. Zugur et al.

Although both species of microorganisms increased the O2 concentration in similar proportions (approximately 150 μmol / L), the onset of production and the time required to reach a plateau at steady state were faster. researchers. This experiment shows that single-celled photosynthetic microorganisms could constitute a new means to increase the supply of oxygen to tissues in a controlled way, both temporally and spatially, under certain ecophysiological conditions or after pathological alterations.

An innovative approach, but not without risk

This approach could be used, for example, to increase oxygen levels in cell cultures, explanted organs or brain slices. But that’s not all: scientists point out that photosynthetic organisms are not only capable of producing oxygen, but also sugars. “It is therefore conceivable that their metabolic pathways could also be harnessed to synthesize nutrients,” explains neurobiologist Hans Straka, a co-author of the study.

Furthermore, since it is possible to control very precisely the intensity, duration and spectrum of the light used, the method could also provide new approaches to the study of the role of oxygen in metabolic processes. But this study is only a proof of principle and it is not certain that these results can actually be translated into treating hypoxic conditions in humans.

As Diana Martinez, a neuroscientist at Rowan University in New Jersey, who was not involved in the study, points out, tadpoles are transparent, meaning that sunlight can easily pass through their skin and into their brains, allowing them to microorganisms carry out photosynthesis.

However, the human skull is not transparent. Therefore, a way should be found to start the process differently. Also, while a lack of oxygen can be a problem, too much oxygen can also make brain damage worse. “The inability to adequately control the oxygen levels generated by these photosynthetic organisms would therefore be as harmful as hypoxia itself,” adds the specialist. Eventually, the microorganisms could grow uncontrollably, until they completely clog the host’s blood vessels …

The study authors also note that a major challenge for a future systemic introduction of phototrophic microorganisms, either in the vascular system or directly in the cerebral ventricular system, is the appearance of a host immune response, as a general reaction to intruders. . Therefore, more studies on possible immune responses are needed to estimate the risks of rejection and the possibility of long-term survival after chronic insertions.

iScience, S. Zugur et al.

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