Astrocytes are cells of the neuroglia, a substance that, unlike neurons, does not conduct electrical signals. They have a different task. They form the blood-brain barrier and maintain the correct environment of the brain parenchyma, for example by regulating pH or ion concentration. In addition, astrocytes supply neurons with nutrients and remove metabolic waste products.

Astrocytes also help control the formation and removal of synapses and provide the substances necessary for producing neurotransmitters, which are crucial for neuronal activity.

'They can, therefore, be called the guardians of the brain. There is virtually no neurological disease associated with astrocyte biology disturbances', says Professor Aleksandra Pękowska, head of the Dioscuri Centre for Chromatin Biology and Epigenomics at the Nencki Institute of Experimental Biology in Warsaw.

Pękowska's team's comprehensive research on the role of astrocytes in brain evolution was published in the prestigious journal „Cell Stem Cell”. 

Previous studies revealed clear differences in mouse, monkey, and human astrocyte morphology (appearance). Human cells are the largest and most complex compared to other species. 'This suggests possible evolutionary changes in Astrocyte function. A larger and more developed brain has larger and more extensive astrocytes', says the researcher, quoted in the press release.

Past research work has been primarily descriptive and focused on astrocytes from mature individuals. Pękowska's team chose foetal cells, however, because the foetal period of human life is a critical time for brain development - many genes known to affect cognition are already or exclusively active at this stage.

'This is why we focused on foetal astrocytes. We obtained them using induced-pluripotent stem cells, which we transformed into astrocytes during the differentiation process', Professor Aleksandra Pękowska explains

Using transcriptomics, a whole-genome approach, the researchers compared gene activity in astrocytes in the three studied species. 'We discovered that a very high percentage of genes that are more active in human than in chimpanzee or macaque astrocytes may be involved in the formation of extracellular vesicles (EV). According to these predictions, we found that human astrocytes produce more EVs than chimpanzee and macaque cells', Pękowska says.

EVs are microscopic biological structures released by living cells into the extracellular space. They are present in all body fluids. EVs do not replicate but provide means for intercellular communication.

'EVs can carry a variety of molecules, such as proteins, lipids, DNA, or RNA. According to some reports they are essential for the proper development of neurons. Since the effect of EVs on astrocytes is poorly understood, we decided to test how vesicles secreted by human astrocytes affect macaque cells', the researcher says. 'It turned out that the monkey cells became larger and more complex under the influence of the human EVs. This means that the particles have transferred some information potentially contributing to the evolution of the morphology (appearance) of the astrocytes. But the mechanism underlying this phenomenon remains unclear', Pękowska points out.

The researchers also found that genes associated with brain diseases are more often 'silenced' than 'activated' in human astrocytes compared to the cells of our ape-like relatives. The silencing of these genes provides our brain with additional functions.

'We do not yet know what these functions are, but gaining them is so valuable that our species is willing to pay a high price - the reduced ability to buffer any changes that lead to further reduction in the activity of these genes. What evolutionary advantage does reducing the activity of genes associated with brain disease give us? This is now the focus of our research,' says Professor Aleksandra Pękowska.

In collaboration with Professor Bartosz Wilczyński from the University of Warsaw, her team combined molecular biology and computational tools including artificial intelligence to show that evolutionary gene activation is linked to well-defined alterations in the DNA sequence.

Scientists at the Nencki Institute are only just beginning their research into the role of astrocyte in brain evolution and the development of cognitive functions. The platform they have developed for acquiring and analysing foetal primate astrocytes, reported in the publication in Cell Stem Cell, opens many possibilities for further analyses.

PAP - Science in Poland

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